EP1520021A2 - Antisense modulation of lrh1 expression - Google Patents

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of Liver Related Homolog-1 (LRH1). The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding LRH1. Methods of using these compounds for modulation of LRH1 expression and for treatment of diseases associated with expression of LRH1 are provided.

Description

ANTISENSE MODULATION OF LRHl EXPRESSION

The present application claims priority under Title 35, United States Code, §119 to United States Provisional application Serial No. 60/392,813, filed July 1 , 2002, which is incorporated by reference in its entirety as if written herein.

FIELD OF THE INVENTION [001] The present invention provides compositions and methods for modulating the expression of Liver Related Homolog-1 (LRHl). In particular, this invention relates to antisense compounds, particularly oligonucleotides, specifically hybridizable with nucleic acids encoding LRHl, Such oligonucleotides have been shown to modulate the expression of LRHl.

BACKGROUND OF THE INVENTION

[002] Cholesterol is essential for a number of cellular processes, including membrane biogenesis and steroid hormone and bile acid biosynthesis. It is the building block for each ofthe major classes of lipoproteins found in cells ofthe human body. Accordingly, cholesterol biosynthesis and catabolism are highly regulated and coordinated processes. A number of diseases and/or disorders have been linked to alterations in cholesterol metabolism or catabolism including atherosclerosis, gall stone formation, and ischemic heart disease. An understanding ofthe pathways involved in cholesterol homeostasis is essential to the development of useful therapeutics for treatment of these diseases and disorders. [003] The metabolism of cholesterol to bile acids represents a major pathway for cholesterol elimination from the body, accounting for approximately half of the daily excretion. These cholesterol metabolites are formed in the liver and secreted into the duodenum ofthe intestine, where they have important roles in the solubilization and absoφtion of dietary lipids and vitamins. Most bile acids (approximately 95%) are subsequently reabsorbed in the ileum and returned to the liver via the enterohepatic circulatory system. [004] Cytochrome 2450 7 A (CYP7 A) is a liver specific enzyme that catalyzes the first and rate-limiting step in one ofthe two pathways for bile acid biosynthesis (Chiang, J.Y.L. 1998. Front. Biosci. 3:176-193; Russell, D.W. and K.D. Setchell. 1992. Biochemistry 31 :4737-4749)'. The gene encoding CYP7A is regulated by a variety of endogenous, small, lipophilic molecules including steroid and thyroid hormones, cholesterol, and bile acids. Notably, CYP7A expression is stimulated by cholesterol feeding and repressed by bile acids. Thus, CYP7A expression is both positively (stimulated or induced) and negatively (inhibited or repressed) regulated. [005] CYP7A expression is regulated by several members ofthe nuclear receptor family of ligand-activated transcription factors (Chiang, J.Y.L. 1998. Front. Biosci. 3:176-193; Gustafsson, J.A. 1999. Science 284:1285-1286; Russell, D.W. 1999. Cell 97:539-542). Recently, two nuclear receptors, the liver X receptor (LXR; NR1H3; Apfel, R. et al. 1994. Mol. Cell. Biol. 14:7025-7035; Willy, P.J. et al. 1995. Genes Devel. 9:1033-1045) and the farnesoid X receptor (FXR; NR1H4; Forman, B.M. et al. 1995. Cell 81:687-693; Seol, W. et al. 1995. Mol. Endocrinol. 9:72-85) were implicated in the positive and negative regulation of CYP7A (Peet, DJ. et al. 1998. Curr. Opin. Genet. Develop. 8:571-575; Russell, D.W. 1999. Cell 97:539- 542) Both LXR and FXR are abundantly expressed in the liver and bind to their cognate hormone response elements as heterodimers with the 9-cis retinoic acid receptor, RXR (Mangelsdorf, D.J. and R.M. Evans. 1995. Cell 83:841-850). [006] LXR is activated by the cholesterol derivative 24,25(S)epoxycholesterol and binds to a response element in the CYP7A promoter (Lehmann, J.M. et al. 1997. J. Biol. Chem. 272:3137-3140). CYP7A is not induced in response to cholesterol feeding in mice lacking LXR (Peet, D.J. et al. 1998. Cell 93:693-704). Moreover, these animals accumulate massive amounts of cholesterol in their livers when fed a high cholesterol diet. These studies establish LXR as a cholesterol sensor responsible for positive regulation of CYP7A expression. [007] Bile acids stimulate the expression of genes involved in bile acid transport such as the intestinal bile acid binding protein (I-BABP) and repress CYP7A as well as other genes involved in bile acid biosynthesis such as CYP8B (which converts chenodeoxycholic acid to cholic acid), and CYP27 (which catalyzes the first step in the alternative pathway for bile acid synthesis)(Javitt, N.B. 1994. FASEB J. 8:1308-1311; Russell, D.W. and K.D. Setchell. 1992. Biochemistry 31 :4737-4749). Recently, FXR was shown to be a bile acid receptor (Makishima, M. et al. 1999. Science 284:1362-1365; Parks, D.J. et al. 1999. Science 284:1365- 1368; Wang, H. 1999. Mol. Cell 3 :543-553). Several different bile acids, including chenodeoxycholic acid and its glycine and taurine conjugates were demonstrated to bind to and activate FXR at physiologic concentrations. In addition, DNA response elements for the FXR/RXR heterodimer were identified in both the human and mouse I-BABP promoters, indicating that FXR mediates positive effects of bile acids on I-BABP expression (Grober, J. et al. 1999. J. Biol. Chem. 274:29749- 29754; Makishima, M. et al. 1999. Science 284:1362-1365). Further, the rank order of bile acids that activate FXR correlates with that for repression of CYP7A in a hepatocyte-derived cell line (Makishima, M. et al. 1999. Science 284:1362-1365). Thus, these studies indicate that FXR also has a role in the negative effects of bile acids on gene expression.

[008] However, the molecular mechanism of bile acid mediated repression of

CYP7A, and specifically the role of FXR has been unclear. Since the CYP7A promoter lacks a strong FXR/RXR binding site (Chiang, J.Y. and D. Stroup. 1994. J. Biol. Chem. 269:17502-17507; Chiang, J.Y. et al. 2000. J. Biol. Chem. 275:10918-10924), it is unlikely that the effect is from the direct interaction of FXR.

[009] An additional nuclear receptor also involved in the expression of

CYP7A is αl-fetoprotein transcription factor (FTF), Cyp7a Promoter Binding

Factor (CPF), Human Bl -Binding Factor (hBlF, B1F, HB1F, HB1F-2) the liver receptor homolog- 1 (LRHl , also called NR5 A2), a monomeric orphan nuclear receptor that functions as a tissue specific transcription factor (Becker- Andre et al 1993. Biochem. Biophys. Res. Comm. 194:1371-1379, Galarneau et al 1996; Mol. Cell. Biol. 16:3853-3865, Li et al 1998. J. Biol. Chem. 273:29022-29031, Nitta et al 1999. Proc. Natl. Acad. Sci. USA 96: 6660-6665. LRHl exists as multiple isoforms that arise via alternative splicing and/or alternative translahonal initiation. The major isoform of LRHl is 495 amino acids in length and is derived from Genbank's provisional mRNA (NM003822). The provisional sequence is obtained from the clones identified by Nitta et al 1999 (CPF :AF 146343) and Li et al 1998 (hBlF:U80251). Additional protein isoforms have been described which include the 541 amino acid "CPF variant 1" containing the same peptide sequence as CPF with a 46 amino acid insertion in the amino-terminus and the 369 amino acid "CPF variant 2" containing a 172 amino acid deletion in its D and E domains (Nitta et al 1998). Galarneau et al 1998 (Cytogenet. Cell Genet. 82, (3-4), 269-270) also described an additional LRH 1 isoform termed FTF (U93553) that is 500 amino acids in length. CPF/hBlF, CPF variant 1, and FTF have been shown to be transcriptionally active where as CPF variant 2 is transcriptionally inactive. Additionally, hBlF/CPF and CPF variants were originally cloned from human liver mRNA libraries and hBlF was found to be expressed in fetal liver, adult liver, and HepG2 cells. (Nitta et al 1999, Li et al 1998). High level expression of LRHl has been shown in the liver, pancreas, and ovary, with less abundant expression in the colon, intestine, and the adrenal gland (Nitta et al 1999, Li et al 1998, Repa and Mangelsdorf, Ann Rev. Cell. Dev. 2000, Wang et al 2001, J. Mol. Endo. 27, 255- 258). Whereas the biological role of each isoform has yet to be elucidated, it is clear that the transcriptionally active isoforms of LRH- 1 are required for hepatic expression of CYP7A and maximize this expression via synergizing with LXR (Nitta et al 1999, Lu et al 2000 Mol. Cell. 6:507-517). LRHl is also required for the expression of short heterodimer partner (SHP, NR0B2), an orphan nuclear receptor that represses transcription and inhibits the function of other nuclear receptors (Seol et al 1996 Science. 272:1336-1339, Johansson, et al 1999 J. Biol. Chem. 274:345-353, Lee et al 1999 J. Biol. Chem. 274:20869-20873). SHP is also a direct gene target of FXR and SHP expression is massively upregulated via FXR agonist compounds including the bile acid CDCA and the synthetic FXR agonist GW4064 (Lu et al 2000, Goodwin et al 2000 Mol. Cell 6: 517-526). Therefore, FXR agonists indirectly repress CYP7a via induction ofthe repressor SHP, which subsequently binds to and represses the transcriptional activity of LRHl on the CYP7A promoter (Lu et al 2000, Goodwin et al 2000). These finding demonstrate the existence of complex regulatory cascades involving LRHl and four other nuclear receptors that coordinately govern bile acid synthesis and cholesterol and lipid homeostasis. [0010] LRHl has also been shown to bind to the enhancer II (ENII) region of the hepatitis B virus (HBV), a transcriptional control region that is essential for the liver specific expression of HBV (Li et al 1998 J. Biol. Chem. 273:29022-29031). HBV is the major cause of acute and chronic hepatitis and is closely associated with the development of hepatocellular carcinoma (Ranye and McLachian (1991) in Molecular Biology ofthe Hepatitus B Virus, ppl-37, CRC Press, Boca Raton, FL). LRHl was shown to drive the transcription from the ENII element of HBV and that mutation ofthe ENII cis-element to which LRHl binds results in the marked loss of transcription. Therefore, LRHl and the ENII has an important role in regulating the transcriptional activity, and consequently, affecting global HBV gene expression (Li at al 1998).

[0011] LRHl has also recently been shown to be highly expressed in human tissues including preadipocytes and primary breast cancer biopsies as well as in human cell lines HepG2 and MCF7. LRHl was also shown to drive expression of the aromatase cytochrome P450 promoter II in the preadipocyte fraction of murine 3T3-L1 preadipocytes (Clyne et al 2002 JBiol. Chem. Papers in Press, 1 April). Breast tumors secrete soluble factors that stimulate aromatase expression via promoter II in breast adipose tissue, thereby increasing esfrogen biosynthesis from C19 steroids. Thus, alterations in the expression or activity of LRHl in adipose tissue could have considerable effects upon local estrogen production with downstream implications on the development and progression of estrogen- dependent breast cancers and carcinogenesis.

[0012] Currently, there are no known therapeutic agents which effectively inhibit the synthesis of LRHl. Consequently, there remains a long felt need for additional agents capable of effectively inhibiting LRHl function. Antisense technology is emerging as an effective means for reducing the expression of specific gene products and may therefore prove to be uniquely useful in a number of therapeutic, diagnostic, and research applications for the modulation of LRHl expression. [00l3] Antisense technology is emerging as an effective means for reducing the expression of specific gene products and may therefore prove to be uniquely useful in a number of therapeutic, diagnostic, and research applications for the modulation of LRHl expression. Systemically administered antisense has been shown to accumulate and have its effect predominately in liver and to a lessor extent in fat (R. S. Geary, R. Z. Yu, and A. A. Levin, "Pharmacokinetics of phosphorothioate antisense oligodeoxynucleotides," Curr. Opin.Investig. Drugs Volume 2, Issue 4, pp. 562-573). Because ofthe liver-specific control of LRH on the expression of CYP7A, this relative tissue specificity of antisense would be useful in the treatment of metabolic disorders.

SUMMARY OF THE INVENTION

[0014] The present invention is directed to antisense compounds, particularly oligonucleotides, which are targeted to a nucleic acid encoding LRHl, and which modulate the expression of LRHl and splice variants thereof. Pharmaceutical and other compositions comprising the antisense compounds ofthe invention are also provided. Further provided are methods of modulating the expression of LRHl in cells or tissues comprising contacting said cells or tissues with one or more ofthe antisense compounds or compositions ofthe invention. Further provided are methods of treating an animal, particularly a human, suspected of having or being prone to a disease or condition associated with expression of LRHl by administering a therapeutically or prophylactically effective amount of one or more ofthe antisense compounds or compositions ofthe invention.

DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention employs oligomeric antisense compounds, particularly oligonucleotides, for use in modulating the function of nucleic acid molecules encoding LRHl, ultimately modulating the amount of LRHlproduced. This is accomplished by providing antisense compounds, which specifically hybridize with one or more nucleic acids encoding LRHl. As used herein, the terms "target nucleic acid" and "nucleic acid encoding LRHl " encompass DNA encoding LRHl , RNA (including pre- mRNA and mRNA) transcribed from such DNA, and also cDNA derived from such RNA. The specific hybridization of an oligomeric compound with its target nucleic acid interferes with the normal function ofthe nucleic acid. This modulation of function of a target nucleic acid by compounds, which specifically hybridize to it, is generally referred to as "antisense". The functions of DNA to be interfered with include replication and transcription. The functions of RNA to be interfered with include all vital functions such as, for example, translocation ofthe RNA to the site of protein translation, translation of protein from the RNA, splicing ofthe RNA to yield one or more mRNA species, and catalytic activity which may be engaged in or facilitated by the RNA. The overall effect of such interference with target nucleic acid function is modulation ofthe expression of LRHl. In the context ofthe present invention, "modulation" means either an increase (stimulation) or a decrease (inhibition) in the expression of a gene. In the context ofthe present invention, inhibition is the preferred form of modulation, of gene expression and mRNA is a preferred target. [0016] It is preferred to target specific nucleic acids for antisense. "Targeting" an antisense compound to a particular nucleic acid, in the context of this invention, is a multistep process. The process usually begins with the identification of a nucleic acid sequence whose function is to be modulated. This may be, for example, a cellular gene (or mRNA transcribed from the gene) whose expression is associated with a particular disorder or disease state, or a nucleic acid molecule from an infectious agent. In the present invention, the target is a nucleic acid molecule encoding LRHl. The targeting process also includes determination of a site or sites within this gene for the antisense interaction to occur such that the desired effect, e.g., detection or modulation of expression ofthe protein, will result. Within the context ofthe present invention, a preferred intragenic site is the region encompassing the translation initiation or termination codon ofthe open reading frame (ORF) ofthe gene. Since, as is known in the art, the translation initiation codon is typically 5'-AUG (in transcribed mRNA molecules; 5'-ATG in the corresponding DNA molecule), the hanslation initiation codon is also referred to as the "AUG codon," the "start codon" or the "AUG start codon". A minority of genes have a translation initiation codon having the RNA sequence 5 '-GUG, 5 '-UUG or 5 '-CUG, and 5 '- AUA, 5'-ACG and 5'-CUG have been shown to function in vivo. Thus, the terms "translation initiation codon" and "start codon" can encompass many codon sequences, even though the initiator amino acid in each instance is typically methionine (in eukaryotes) or formyl methionine (in prokaryotes). It is also known in the art that eukaryotic and prokaryotic genes may have two or more alternative start codons, any one of which may be preferentially utilized for translation initiation in a particular cell type or tissue, or under a particular set of conditions. In the context ofthe invention, "start codon" and "translation initiation codon" refer to the codon or codons that are used in vivo to initiate translation of an mRNA molecule transcribed from a gene encoding LRHl, regardless ofthe sequence(s) of such codons. [0017] It is also known in the art that a translation termination codon (or "stop codon") of a gene may have one of three sequences, i.e. 5'-UAA, 5'- UAG and 5'-UGA (the corresponding DNA sequences are 5'-TAA, 5 '-TAG and 5'-TGA, respectively). The terms "start codon region" and "translation initiation codon region "refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5' or 3') from a translation initiation codon. Similarly, the terms "stop codon region" and "translation termination codon region "refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5' or 3') from a translation termination codon.

[0018] The open reading frame (ORF) or "coding region," which is known in the art to refer to the region between the translation initiation codon and the translation termination codon, is also a region which may be targeted effectively. Other target regions include the 5 ' untranslated region (5 'UTR), known in the art to refer to the portion of an mRNA in the 5' direction from the translation initiation codon, and thus including nucleotides between the 5' cap site and the translation initiation codon of an mRNA or corresponding nucleotides on the gene, ahd the 3' untranslated region (3 'UTR), known in the art to refer to the portion of an mRNA in the 3' direction from the translation termination codon, and thus including nucleotides between the translation termination codon and 3' end of an mRNA or corresponding nucleotides on the gene. The 5' cap of an mRNA comprises an N7-methylated guanosine residue joined to the 5 '-most residue ofthe mRNA via a 5 '-5' triphosphate linkage. The 5' cap region of an mRNA is considered to include the 5' cap structure itself as well as the first 50 nucleotides adjacent to the cap. The 5' cap region may also be a preferred target region. [0019] Although some eukaryotic mRNA transcripts are directly translated, many contain one or more regions, known as "introns," which are excised from a transcript before it is translated. The remaining (and therefore translated) regions are known as "exons" and are spliced together to form a continuous mRNA sequence. mRNA splice sites, i.e., intron-exon junctions, may also be preferred target regions, and are particularly useful in situations where aberrant splicing is implicated in disease, or where an overproduction of a particular mRNA splice product is implicated in disease. Aberrant fusion junctions due to rearrangements or deletions are also preferred targets. It has also been found that introns can also be effective, and therefore preferred, target regions for antisense compounds targeted, for example, to DNA or pre-mRNA. [0020] Once one or more target sites have been identified, oligonucleotides are chosen which are sufficiently complementary to the target, i.e., hybridize sufficiently well and with sufficient specificity, to give the desired effect.

[0021] In the context of this invention, "hybridization" means hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nucleotide bases. For example, adenine and thymine are complementary nucleobases, which pair through the formation of hydrogen bonds. "Complementary," as used herein, refers to the capacity for precise pairing between two nucleotides. For example, if a nucleotide at a certain position of an oligonucleotide is capable of hydrogen bonding with a nucleotide at the same position of a DNA or RNA molecule, then the oligonucleotide and the DNA or RNA are considered to be complementary to each other at that position. The oligonucleotide and the DNA or RNA are complementary to each other when a sufficient number of corresponding positions in each molecule are occupied by nucleotides which can hydrogen bond with each other. Thus, "specifically hybridizable" and "complementary" are terms which are used to indicate a sufficient degree of complementarity or precise pairing such that stable and specific binding occurs between the oligonucleotide and the DNA or RNA target. It is understood in the art that the sequence of an antisense compound need not be 100% complementary to that of its target nucleic acid to be specifically hybridizable. An antisense compound is specifically hybridizable when binding of the compound to the target DNA or RNA molecule interferes with the normal function ofthe target DNA or RNA to cause a loss of utility, and there is a sufficient degree of complementarity to avoid non-specific binding ofthe antisense compound to non-target sequences under conditions in which specific binding is desired, i.e., under physiological conditions in the case of in vivo assays or therapeutic treatment, and in the case of in vitro assays, under conditions in which the assays are performed.

[0022] Antisense compounds are commonly used as research reagents and diagnostics. For example, antisense oligonucleotides, which are able to inhibit gene expression with exquisite specificity, are often used by those of ordinary skill to elucidate the function of particular genes. Antisense compounds are also used, for example, to distinguish between functions of various members of a biological pathway. Antisense modulation has, therefore, been harnessed for research use. [0023] The specificity and sensitivity of antisense is also harnessed by those of skill in the art for therapeutic uses. Antisense oligonucleotides have been employed as therapeutic moieties in the treatment of disease states in animals and man. Antisense oligonucleotides have been safely and effectively administered to humans and numerous clinical trials are presently underway. It is thus established that oligonucleotides can be useful therapeutic modalities that can be configured to be useful in treatment regimes for treatment of cells, tissues and animals, especially humans. In the context of this invention, the term "oligonucleotide" refers to an oligomer or polymer of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) or mimetics thereof. This term includes oligonucleotides composed of naturally occurring nucleobases, sugars and covalent internucleoside (backbone) linkages as well as oligonucleotides having non-naturally occurring portions which function similarly. Such modified or substituted oligonucleotides are often preferred over native forms because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for nucleic acid target and increased stability in the presence of nucleases. [0024] While antisense oligonucleotides are a preferred form of antisense compound, the present invention comprehends other oligomeric antisense compounds, including but not limited to oligonuclectide mimetics such as are described below. The antisense compounds in accordance with this invention preferably comprise from about 8 to about 30 nucleobases (i.e. from about 8 to about 30 linked nucleo sides). Particularly preferred antisense compounds are antisense oligonuclectides, even more preferably those comprising from about 12 to about 25 nucleobases. As is known in the art, a nucleoside is a base-sugar combination. The base portion ofthe nucleoside is normally a heterocyclic base. The two most common classes of such heterocyclic bases are the purines and the pyrimidines. Nucleotides are nucleosides that further include a phosphate group covalently linked to the sugar portion ofthe nucleoside. For those nucleosides that include a ' pentofuranosyl sugar, the phosphate group can be linked to either the 2', 3' or 5 'hydroxyl moiety ofthe sugar. In forming oligonucleotides, the phosphate groups covalently link adjacent nucleosides to one another to form a linear polymeric compound. In turn the respective ends of this linear polymeric structure can be further joined to form a circular structure, however, open linear structures are generally preferred. Within the oligonucleotide structure, the phosphate groups are .commonly referred to as forming the internucleoside backbone ofthe oligonucleotide. The normal I linkage or backbone of RNA and DNA is a 3' to 5' phosphodiester linkage. [0025] Specific examples of preferred antisense compounds useful in this invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. As defined in this specification, oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides.

[0026] Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3 'alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3 '-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3 '-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts and free acid forms are also included.

[0027] Representative United States patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S.: 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050, each of which is herein incorporated by reference.

[0028] Preferred modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH₂ component parts.

[0029] Representative United States patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S.: 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439, each of which is herein incorporated by reference.

[0030] In other preferred oligonucleotide mimetics, both the sugar and the internucleoside linkage, i.e., the backbone, ofthe nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound, one such oligomeric compound, an oligonucleotide mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms ofthe amide portion ofthe backbone. Representative United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S.: 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al., Science, 1991, 254, 1497-1500.

[0031] Most preferred embodiments of the invention are oligonucleotides with phosphorothioate backbones and oligonucleosides with heteroatom backbones, and in particular -CH₂-NH-O-CH₂-, -CH₂-N (CH₃) -O-CH₂- [known as a methylene (methylimino) or MMI backbone] , - CH₂-O-N (CH₃) -CH₂-, -CH₂N(CH₃)-N(CH₃)-CH₂- and -O-N(CH₃)-CH₂- CH₂- [wherein the native phosphodiester backbone is represented as -O-P- O-CH2-] ofthe above referenced U.S. patent 5,489,677, and the amide backbones ofthe above referenced U.S. patent 5,602,240. Also preferred are oligonucleotides having morpholino backbone structures ofthe above- referenced U.S. patent 5,034,506.

[0032] Modified oligonucleotides may also contain one or more substituted sugar moieties. Preferred oligonucleotides comprise one ofthe following at the 2' position: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted d to C₁₀ alkyl or C₂ to C₁₀ alkenyl and alkynyl. Particularly preferred are O[(CH₂)_nO]_mCH₃, O(CH₂)„,OCH₃, O(CH₂)„NH₂, O(CH₂)„CH₃, O(CH₂)_nONH₂, and O(CH_2nON[(CH₂)_nCH₃)]2 where n and m are from 1 to about 10. Other preferred oligonucleotides comprise one ofthe following at the 2' position: to do, ( lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH₃, OCN, CI, Br, CN, CF₃, OCF₃, SOCH₃, SO₂CH₃, ON0₂, NO₂, N₃, NH2, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. A preferred modification includes 2' -methoxyethoxy ( -O-CH₂CH₂OCH₃, also known as 2'-O- (2- methoxyethyl) or 2'-MOE) (Martin et al., Helv. Chim. Ada, 1995, 78, 486- 504) i.e., an alkoxyalkoxy group. A further preferred modification includes 2'-dimethylaminooxyethoxy, i.e., a O(CH₂)₂O (CH₃)₂ group, also known as 2'-DMAOE, as described in examples herein below, and 2'- dimethylaminoethoxyethoxy (also known in the art as 2'-O- dimethylaminoethoxyethyl or 2'-DMAEOE), i.e., 2'-O-CH₂-O-CH.-N (CH₂)₂, also described in examples herein below.

[0033] Other preferred modifications include 2'-methoxy (2'-O CH₃) , 2'-aminopropoxy (2'-O CH₂ CH₂ CH₂NH₂) and 2'-fluoro (2'-F). Similar modifications may also be made at other positions on the oligonucleotide, particularly the 3' position ofthe sugar on the 3' terminal nucleotide or in 2'-5 ' linked oligonucleotides and the 5 ' position of 5 ' terminal nucleotide. Oligonucleotides may also have sugar mimetics such as cyclobutyl moieties in place ofthe pentofuranosyl sugar. Representative United States patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S.: 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; and 5,700,920, each of which is herein incorporated by reference in its entirety. [0034] Oligonucleotides may also include nucleobase (often referred to in the art simply as "base") modifications or substitutions. As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5- halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5 -halo particularly 5-bromo, 5 -trifluoromethyl and other 5- substituted uracils and cytosines, 7-methylquanine and 7-methyladenine, 8- azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3- deazaguanine and 3-deazaadenine. Further nucleobases include those disclosed in United States Patent No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858- 859, Kroschwitz, J.I., ed. John Wiley & Sons, 1990, those disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y.S., Chapter 15, Antisense Research and Applications, pages 289-302, Crooke, S.T. and Lebleu, B. ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity ofthe oligomeric compounds ofthe invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2°C (Sanghvi, Y.S., Crooke, S.T. and Lebleu, B., eds, Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions, even more particularly when combined with 2'-O- methoxyethyl sugar modifications. [0035] Representative United States patents that teach the preparation of certain ofthe above noted modified nucleobases as well as other modified nucleobases include, but are not limited to, the above noted U.S. 3,687,808, as well as U.S.: 4,845,205; 5,130,302; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,12', 5,596,091; 5,614,617; 5,750,692; and 5,681,941, each of which is herein incorporated by reference. [0036] Another modification of the oligonucleotides of the invention involves chemically linking to the oligonucleotide one or more moieties or conjugates, which enhance the activity, cellular distribution or cellular uptake ofthe oligonucleotide. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556), cholic acid (Manoharan et al., Bioorg. Med. Chem. Let, 1994, 4, 1053-1060), a thioether, e.g., hexyl-S- tritylthiol (Manoharan et al., Ann. N. Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al, EMBOJ., 1991, 10, 1111-1118; Kabanov et al., E5S Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phosphohpid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1 ,2-di-O-hexadecyl- rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 365'-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Mancharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 365 '-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Ada, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937).

[0037] Representative United States patents that teach the preparation of such oligonucleotide conjugates include, but are not limited to, U.S.:

4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730;

5,552,538; 5,578,717, 5,580,731; 5,580,731; 5,591,584; 5,109,124;

5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737;

4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830;

5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022;

5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098;

5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371;

5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941, each of which is herein incoφorated by reference.

[0038] It is not necessary for all positions in a given compound to be uniformly modified, and in fact more than one ofthe aforementioned modifications may be incoφorated in a single compound or even at a single nucleoside within an oligonucleotide. The present invention also includes antisense compounds, which are chimeric compounds. "Chimeric" antisense compounds or "chimeras," in the context of this invention, are antisense compounds, particularly oligonucleotides, which contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nucleotide in the case of an oligonucleotide compound. These oligonucleotides typically contain at least one region wherein the oligonucleotide is modified so as to confer upon the oligonucleotide increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid. An additional region ofthe oligonucleotide may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNase H is a cellular endonuclease, which cleaves the RNA strand of RNA:DNA duplex. Activation of RNase H, therefore, results in cleavage ofthe RNA target, thereby greatly enhancing the efficiency of oligonucleotide inliibition of gene expression. Consequently, comparable results can often be obtained with shorter oligonucleotides when chimeric oligonucleotides are used, compared to phosphorothioate deoxyoligonucleotides hybridizing to the same target region. Cleavage ofthe RNA target can be routinely detected by gel electrophoresis and, if necessary, associated nucleic acid hybridization techniques known in the art.

[0039] Chimeric antisense compounds ofthe invention may be formed as composite structures of two or more oligonucleotides, modified oligonucleotides, oligonucleosides and/or oligonucleotide mimetics as described above. Such compounds have also been referred to in the art as hybrids or gapmers. Representative United States patents that teach the preparation of such hybrid structures include, but are not limited to, U.S.: 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711; 5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922, each of which is herein incoφorated by reference in its entirety. [0040] The antisense compounds used in accordance with this invention may be conveniently, and routinely made through the well-known technique of solid phase synthesis. Equipment for such synthesis is sold by several vendors including, for example, Applied Biosystems (Foster City, CA). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is well known to use similar techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives. [0041] The antisense compounds ofthe invention are synthesized in vitro and do not include antisense compositions of biological origin, or genetic vector constructs designed to direct the in vivo synthesis of antisense molecules. The compounds ofthe invention may also be admixed, encapsulated, conjugated or otherwise associated with other molecules, molecule structures or mixtures of compounds, as for example, liposomes, receptor targeted molecules, oral, rectal, topical or other formulations, for assisting in uptake, distribution and/or absoφtion. Representative United States patents that teach the preparation of such uptake, distribution and/or absoφtion assisting formulations include, but are not limited to, U.S.: 5,108,921; 5,354,844; 5,416,016; 5,459,127; 5,521,291; 5,543,158; 5,547,932; 5,583,020; 5,591,721; 4,426,330; 4,534,899; 5,013,556; 5,108,921; 5,213,804; 5,227,170; 5,264,221; 5,356,633; 5,395,619; 5,416,016; 5,417,978; 5,462,854; 5,469,854; 5,512,295; 5,527,528; 5,534,259; 5,543,152; 5,556,948; 5,580,575; and 5,595,756, each of which is herein incoφorated by reference. [0042] The antisense compounds ofthe invention encompass any pharmaceutically acceptable salts, esters, or salts of such esters, or any other compound which, upon administration to an animal including a human, is capable of providing (directly or indirectly) the biologically active metabolite or residue thereof. Accordingly, for example, the disclosure is also drawn to prodrugs and pharmaceutically acceptable salts ofthe compounds ofthe invention, pharmaceutically acceptable salts of such prodrugs, and other bioequivalents. [0043] The tenn "prodrug" indicates a therapeutic agent that is prepared in an inactive form that is converted to an active form (i.e., drug) within the body or cells thereof by the action of endogenous enzymes or other chemicals and/or conditions. In particular, prodrug versions ofthe oligonuclectides ofthe invention are prepared as SATE [(S-acetyl-2- thioethyl) phosphate] derivatives according to the methods disclosed in WO 93/24510 to Gosselin et al., published December 9, 1993 or in WO 94/26764 to Imbach et al.

[0044] The term "pharmaceutically acceptable salts" refers to physiologically and pharmaceutically acceptable salts ofthe compounds of the invention: i.e., salts that retain the desired biological activity ofthe parent compound and do not impart undesired toxicological effects thereto. [0045] Pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Examples of metals used as cations are sodium, potassium, magnesium, calcium, and the like. Examples of suitable amines are N, N'- dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, dicyclohexylamine, ethylenediamine, N-methylglucamine, and procaine (see, for example, Berge et al., "Pharmaceutical Salts," J. ofPharma Sci., 1977, 66, 119). The base addition salts of said acidic compounds are prepared by contacting the free acid form with a sufficient amount ofthe desired base to produce the salt in the conventional manner. The free acid form may be regenerated by contacting the salt form with an acid and isolating the free acid in the conventional manner. The free acid forms differ from their respective salt forms somewhat in certain physical properties such as solubility in polar solvents, but otherwise the salts are equivalent to their respective free acid for pmposes of the present invention. As used herein, a "pharmaceutical addition salt" includes a pharmaceutically acceptable salt of an acid form of one ofthe components ofthe compositions ofthe invention. These include organic or inorganic acid salts ofthe amines. Preferred acid salts are the hydrochlorides, acetates, salicylates, nitrates and phosphates. Other suitable pharmaceutically acceptable salts are well known to those skilled in the art and include basic salts of a variety of inorganic and organic acids, such as, for example, with inorganic acids, such as for example hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid; with organic carboxylic, sulfonic, sulfo or phospho acids or N-substituted sulfamic acids, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, lactic acid, oxalic acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2- phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid; and with amino acids, such as the 20 alpha-amino acids involved in the synthesis of proteins in nature, for example glutamic acid or aspartic acid, and also with phenylacetic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, ethane- 1 ,2-disulfonic acid, benzenesulfonic acid, 4-methylbenzenesulfoic acid, naphthalene-2- sulfonic acid, naphthalene- 1, 5 -disulfonic acid, 2- or 3 -phosphogly cerate, glucose-6-phosphate, N-cyclohexylsulfamic acid (with the formation of cyclamates), or with other acid organic compounds, such as ascorbic acid. Pharmaceutically acceptable salts of compounds may also be prepared with ^' a pharmaceutically acceptable cation. Suitable pharmaceutically acceptable cations are well known to those skilled in the art and include alkaline, alkaline earth, ammonium and quaternary ammonium cations. Carbonates or hydrogen carbonates are also possible. [0046] For oligonucleotides, preferred examples of pharmaceutically acceptable salts include but are not limited to (a) salts formed with cations such as sodium, potassium, ammonium, magnesium, calcium, polyamines such as spermine and spermidine, etc.; (b) acid addition salts formed with inorganic acids, for example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like; (c) salts formed with organic acids such as, for example, acetic acid, oxalic acid, tartaric acid, succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, methanesulfonic acid, p- toluenesulfonic acid, naphthalenedisulfonic acid, polygalacturonic acid, and the like; and (d) salts formed from elemental anions such as chlorine, bromine, and iodine.

[0047] The antisense compounds ofthe present invention can be utilized for diagnostics, therapeutics, prophylaxis and as research reagents and kits. For therapeutics, an animal, preferably a human, suspected of having a disease or disorder, which can be treated by modulating the expression of LRHl, is treated by administering antisense compounds in accordance with this invention. The compounds ofthe invention can be utilized in pharmaceutical compositions by adding an effective amount of an antisense compound to a suitable pharmaceutically acceptable diluent or carrier. Use ofthe antisense compounds and methods ofthe invention may also be useful prophylactically, e.g., to prevent or delay infection, inflammation or tumor formation, for example. [0048] The antisense compounds ofthe invention are useful for research and diagnostics, because these compounds hybridize to nucleic acids encoding LRHl , enabling sandwich and other assays to easily be constructed to exploit this fact. Hybridization ofthe antisense oligonucleotides ofthe invention with a nucleic acid encoding LRHl can be detected by means known in the art. Such means may include conjugation of an enzyme to the oligonucleotide, radiolabelling ofthe oligonucleotide or any other suitable detection means. Kits using such detection means for detecting the level of LRHl in a sample may also be prepared. [0049] The present invention also includes pharmaceutical compositions and formulations, which include the antisense compounds ofthe invention. The pharmaceutical compositions ofthe present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical (including ophthalmic and to mucous membranes including vaginal and rectal delivery), pulmonary, e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Oligonucleotides with at least one 2'-O- methoxyethyl modification are believed to be particularly useful for oral administration.

[0050] Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Coated condoms, gloves and the like may also be useful.

[0051] Compositions and formulations for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets or tablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable.

[0052] Compositions and formulations for parenteral, intrathecal or intraventricular administration may include sterile aqueous solutions, which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients. [0053] Pharmaceutical compositions ofthe present invention include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self- emulsifying solids and self-emulsifying semisolids.

[0054] The pharmaceutical formulations ofthe present invention, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.

[0055] The compositions ofthe present invention may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions ofthe present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances, which increase the viscosity ofthe suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers. [0056] In one embodiment ofthe present invention the pharmaceutical compositions may be formulated and used as foams. Pharmaceutical foams include formulations such as, but not limited to, emulsions, microemulsions, creams, jellies and liposomes. While basically similar in nature these formulations vary in the components and the consistency ofthe final product. The preparation of such compositions and formulations is generally known to those skilled in the pharmaceutical and formulation arts and may be applied to the formulation ofthe compositions ofthe present invention. Emulsions

[0057] The compositions of the present invention may be prepared and formulated as emulsions. Emulsions are typically heterogenous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1 μm in diameter. (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, i Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1 , p. 245; Block in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335; Higuchi et al., in Remington 's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 1985, p. 301). Emulsions are often biphasic systems comprising of two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be either water-in-oil (w/o) or ofthe oil-in-water (o/w) variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase the resulting composition is called a water-in-oil (w/o) emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase the resulting composition is called an oil-in-water (o/w) emulsion. Emulsions may contain additional components in addition to the dispersed phases and the active drug, which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase. Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil- in-water-in-oil (o/w/o) and water-in-oil-in- water (w/o/w) emulsions. Such complex formulations often provide certain advantages that simple binary emulsions do not. Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion. Likewise a system of oil droplets enclosed in globules of water stabilized in an oily continuous provides an o/w/o emulsion. [0058] Emulsions are characterized by little or no thermodynamic stability. Often, the dispersed or discontinuous phase ofthe emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity ofthe formulation. Either ofthe phases ofthe emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incoφorated into either phase ofthe emulsion. Emulsifiers may broadly be classified into four categories: synthetic surfactants, naturally occurring emulsifiers, absoφtion bases, and finely dispersed solids (Idson, in Pharmaceutical Dosaqe Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , p. 199). [0059] Synthetic surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , p. 285; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion. The ratio ofthe hydrophilic to the hydrophobic nature ofthe surfactant has been tenned the hydrophile/lipophile balance (HLB) and is a valuable tool in categorizing and selecting surfactants in the preparation of formulations. Surfactants may be classified into different classes based on the nature ofthe hydrophilic group: nonionic, anionic, cationic and amphoteric (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285).

[0060] Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia. Absoφtion bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations. These include polar inorganic solids, such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate.

[0061] A large variety of non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives, and antioxidants (Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , p. 199).

[0062] Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersedphase droplets and by increasing the viscosity ofthe external phase. [0063] Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides that may readily support the growth of microbes, these formulations often incoφorate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid. Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.

[0064] The application of emulsion formulations via dermatological, oral and parenteral routes and methods for their manufacture have been reviewed in the literature (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New

York, N.Y., volume 1, p. 199). Emulsion formulations for oral delivery have been very widely used because of reasons of ease of formulation, efficacy from an absoφtion and bioavailability standpoint. (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Mineral-oil base laxatives, oil-soluble vitamins and high fat nutritive preparations are among the materials that have commonly been administered orally as o/w emulsions.

[0065] In one embodiment ofthe present invention, the compositions of oligonucleotides and nucleic acids are formulated as microemulsions. A microemulsion may be defined as a system of water, oil and amphiphile, which is a single optically isotropic, and thermodynamically stable liquid solution (Rosoff, in Pharmaceutical Dosage Forms, Liebeπnan, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Typically microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain- length alcohol to form a transparent system. Therefore, microemulsions have also been described as thermodynamically stable, isotropically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in: Controlled Release of Drugs: Polymers and Aggregate Systems, Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 1852'5). Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte. Whether the microemulsion is ofthe water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties ofthe oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington 's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 1985, p. 271).

[0066] The phenomenological approach utilizing phase diagrams has been extensively studied and has yielded a comprehensive knowledge, to one skilled in the art, of how to formulate microemulsions (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335). Compared to conventional emulsions, microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously.

[0067] Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (S0750), decaglycerol decaoleate (DAO750), alone or in combination with cosurfactants. The cosurfactant, usually a short-chain alcohol such as ethanol, 1 -propanol, and 1 -butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because ofthe void space generated among surfactant molecules. Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art. The aqueous phase may typically be, but is not limited to, water, an aqueous solution ofthe drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol. The oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and triglycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil. [0068] Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absoφtion of drugs. Lipid based microemulsions (both o/w and w/o) have been proposed to enhance the oral bioavailability of drugs, including peptides (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385-1390; Ritschel, Meth. Find. Exp. Clin. Pharmacol, 1993, 13, 205). Microemulsions afford advantages of improved drag solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absoφtion due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385; Ho et al., J. Pharm. Sci., 1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or oligonucleotides. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications. It is expected that the microemulsion compositions and formulations ofthe present invention will facilitate the increased systemic absoφtion of oligonucleotides and nucleic acids from the gastrointestinal tract, as well as improve the local cellular uptake of oligonucleotides and nucleic acids within the gastrointestinal tract, vagina, buccal cavity and other areas of administration. [0069] Microemulsions ofthe present invention may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties ofthe formulation and to enhance the absoφtion ofthe oligonucleotides and nucleic acids ofthe present invention. Penetration enhancers used in the microemulsions ofthe present invention may be classified as belonging to one of five broad categories - surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of these classes has been discussed above.

[0070] Liposomes

[0071] There are many organized surfactant structures besides microemulsions that have been studied and used for the formulation of drugs. These include monolayers, micelles, bilayers and vesicles. Vesicles, such as liposomes, have attracted great interest because of their specificity and the duration of action they offer from the standpoint of drug delivery. As used in the present invention, the term "liposome" means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers. [0072] Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Noncationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo. [0073] In order to cross intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a liposome, which is highly deformable and able to pass through such fine pores.

[0074] Further advantages of liposomes include; liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incoφorate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, P. 245). Important considerations in the preparation of liposome formulations are the lipid surface charge, vesicle size and the aqueous volume ofthe liposomes.

[0075] Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes. As the merging ofthe liposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act. [0076] Liposomal formulations have been the focus of extensive investigation as the mode of delivery for many drugs. There is growing evidence that for topical administration, liposomes present several advantages over other formulations. Such advantages include reduced side- effects related to high systemic absoφtion ofthe administered drug, increased accumulation ofthe administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin.

[0077] Several reports have detailed the ability of liposomes to deliver agents including high-molecular weight DNA into the skin. Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting ofthe upper epidermis.

[0078] Liposomes fall into two broad classes. Cationic liposomes are positively charged liposomes, which interact with the negatively charged DNA molecules to form a stable complex. The positively charged

DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al., Biochem. Biophys. Res. Commun., 1987, 147, 980 - 985) [0079] Liposomes, which are pH-sensitive or negatively-charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression ofthe exogenous gene was detected in the target cells (Zhou et al., Journal of Controlled Release, 1992, 19, 269-274).

[0080] One major type of liposomal composition includes phospholipids other than naturally-derived phosphatidyl choline. Neutral liposome compositions, for example, can be formed from dimyristoyl phosphatidyl choline (DMPC) or dipalmitoyl phosphatidyl choline (DPPC). Anionic liposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE). Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC. Another type is formed from mixtures of phosphohpid and/or phosphatidylcholine and/or cholesterol. [0081] Several studies have assessed the topical delivery of liposomal drug formulations to the skin. Application of liposomes containing interferon to guinea pig skin resulted in a reduction of skin heφes sores while delivery of interferon via other means (e.g. as a solution or as an emulsion) were ineffective (Weiner et al., Journal of Drug Targeting, 1992, 2, 405-410). Further, an additional study tested the efficacy of interferon administered as part of a liposomal formulation to the administration of interferon using an aqueous system, and concluded that the liposomal formulation was superior to aqueous administration (du Plessis et al., Antiviral Research, 1992, 18, 259-265).

[0082] Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol. Non-ionic liposomal formulations comprising Novasome ™ I (glyceryl dilaurate/cholesterol/polyoxyethylene-10-stearyl ether) and Novasome™ II (glyceryl distearate/ cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers ofthe skin (Hu et al. S.TP.Pharma. Sci., 1994, 4, 6, 466).

[0083] Liposomes also include "sterically stabilized" liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incoφorated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking sμch specialized lipids. Examples of sterically stabilized liposomes are those in which part ofthe vesicle-forming lipid portion ofthe liposome (A) comprises one or more glycolipids, such as monosialoganglioside G _I, or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. While not wishing to be bound by any particular theory, it is thought in the art that, at least for sterically stabilized liposomes containing gangliosides, sphingomyelin, or PEG-derivatized lipids, the enhanced circulation half-life of these sterically stabilized liposomes derives from a reduced uptake into cells ofthe reticuloendothehal system (RES) (Allen et al., FEBS Letters, 1987, 223, 42; Wu et al., Cancer Research, 1993, 53, 3765).

[0084] Various liposomes comprising one or more glycolipids are known in the art. Papahadjopoulos et al. (Ann. NY. Acad. Sci., 1987, 507, 64) reported the ability of monosialoganglioside G_M], galactocerebroside sulfate and phosphatidylinositol to improve blood half-lives of liposomes. These findings were expounded upon by Gabizon et al. (Proc. Natl. Acad. Sci. U.S.A., 1988, 85, 6949). U.S. Patent No. 4,837,028 and WO 88/04924, both to Allen et al., disclose liposomes comprising (1) sphingomyelin and (2) the ganglioside Gjor a galactocerebroside sulfate ester. U.S. Patent No. 5,543,152 (Webb et al.) discloses liposomes comprising sphingomyelin. Liposomes comprising 1 ,2-sn-dimyristoylphosphatidylcholine are disclosed in WO 97/13499 (Lim et al.).

[0085] Many liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art. Sunamoto et al. (Bull. Chem. Soc. Jpn., 1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C₁₂15G, that contains a PEG moiety. Ilium et al. (FEBS Lett., 1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives. Synthetic phospholipids modified by the attachment of carboxylic groups of poly alkylene glycols (e.g., PEG) are described by Sears (U.S. Patent Nos. 4,426,330 and 4,534,899). Klibanov et al. (FEBS Lett., 1990, 268, 235) described experiments demonstrating that liposomes comprising phosphatidylethanolamine (PE) derivatized with PEG or PEG stearate have significant increases in blood circulation half-lives. Blume et al. (Biochimica et Biophysica Acta, 1990, 1029, 91) extended such observations to other PEGderivatized phospholipids, e.g., DSPE-PEG, formed from the combination of distearoylphosphatidylethanolamine (DSPE) and PEG. Liposomes having covalently bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 Bl and WO 90/04384 to Fisher. Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Patent Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Patent No. 5,213,804 and European Patent No. EP 0 496 813 Bl). Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Patent No. 5,225,212 (both to Martin et al.) and in WO 94/20073 (Zalipsky et al.) Liposomes comprising PEG-modified ceramide lipids are described in WO 96/10391 (Choi et al.). U.S. Patent Nos. 5,540,935 (Miyazaki et al.) and 5,556,948 (Tagawa et al.) describe PEG- containing liposomes that can be further derivatized with functional moieties on their surfaces.

[0086] A limited number of liposomes comprising nucleic acids are known in the art. WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes. U.S. Patent No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include an antisense RNA. U.S. Patent No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love et al. discloses liposomes comprising antisense oligonucleotides targeted to the rafgene.

[0087] Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets which are so highly deformable that they are easily able to penehate through pores which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g. they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin. [0088] Surfactants find wide application in formulations such as emulsions (including microemulsions) and liposomes. The most common way of classifying and ranking the properties ofthe many different types of surfactants, both natural and synthetic, is by the use ofthe hydrophile/lipophile balance (HLB). The nature ofthe hydrophilic group (also known as the "head") provides the most useful means for categorizing the different surfactants used in formulations (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, NY, 1988, p. 285) [0089] If the surfactant molecule is not ionized, it is classified as a nonionic surfactant. Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general their HLB values range from 2 to about 18 depending on their structure. Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters. Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class. The polyoxyethylene surfactants are the most popular members of the nonionic surfactant class. [0090] If the surfactant molecule carries a negative charge when it is dissolved or dispersed in water, the surfactant is classified as anionic. Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates. The most important members ofthe anionic surfactant class are the alkyl sulfates and the soaps.

[0091] If the surfactant molecule carries a positive charge when it is dissolved or dispersed in water, the surfactant is classified as cationic. Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class.

[0092] If the surfactant molecule has the ability to carry either a positive or negative charge, the surfactant is classified as amphoteric. Amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N- alkylbetaines and phosphatides.

[0093] The use of surfactants in drug products, formulations and in emulsions has been reviewed (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, NY, 1988, p. 285). Penetration Enhancers [0094] In one embodiment, the present invention employs various penetration enhancers to effect the efficient delivery of nucleic acids particularly oligonucleotides, to the skin of animals. Most drugs are present in solution in both ionized and nonionized forms. However, usually only lipid soluble or lipophilic drugs readily cross cell membranes. It has been discovered that even non-lipophilic drugs may cross cell membranes if the membrane to be crossed is treated with a penetration enhancer. In addition to aiding the diffusion of non-lipophilic drugs across cell membranes, penetration enhancers also enhance the permeability of lipophilic drugs. [0095] Penetration enhancers may be classified as belonging to one of five broad categories, i.e., surfactants, fatty acids, bile salts, chelating agents, and non-chelating nonsurfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92). Each ofthe above mentioned classes of penetration enhancers are described below in greater detail. [0096] Surfactants: In connection with the present invention, surfactants (or "surface-active agents") are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension ofthe solution or the interfacial tension between the aqueous solution and another liquid, with the result that absoφtion of oligonucleotides through the mucosa. is enhanced. In addition to bile salts and fatty acids, these penetration enhancers include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92); and perfluorochemical emulsions, such as FC-43. Takahashi et al., J. Pharm. Pharmacol., 1988, 40, 252). [0097] Fatty acids: Various fatty acids and their derivatives which act as penetration enhancers include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (l-monooleoyl-.rac- glycerol), dilaurin, caprylic acid, arachidonic acid, glycerol 1-monocaprate, l-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines, C_rl0 alkyl esters thereof (e.g., methyl, isopropyl and t-butyl), and mono- and di- glycerides thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; El Hariri et al., J. Pharm. Pharmacol, 1992, 44, 651-654).

[0098] Bile salts: The physiological role of bile, includes the facilitation of dispersion and absoφtion of lipids and fat-soluble vitamins (Brunton, Chapter 38 in: Goodman & Gilman 's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al. Eds. McGraw-Hill, New York, 1996, pp. 934-935). Various natural bile salts, and their synthetic derivatives, act as penetration enhancers. Thus the term "bile salts" includes any ofthe naturally occurring components of bile as well as any of their synthetic derivatives. The bile salts ofthe invention include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxychohc acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate

(STDHF), sodium glycodihydrofusidate'and polyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Swinyard, Chapter 39 In: Remington 's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, PA, 1990, pages 782-783; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Yamamoto et al., J. Pharm. Exp. Ther., 1992, 263, 25; Yamashita et al., J. Pharm. Sci., 1990, 79, 579-583). [0099] Chelating Agents: Chelating agents, as used in connection with the present invention, can be defined as compounds that remove metallic ions from solution by forming complexes therewith, with the result that absoφtion of oligonucleotides through the mucosa is enhanced. With regards to their use as penetration enhancers in the present invention, chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett, J.

Chromatogr., 1993, 618, 315-339). Chelating agents ofthe invention include but are not limited to disodium. ethylenediaminetetraacetate (EDTA), citric acid, sahcylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of beta-diketpnes (enamines)(Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Buur et al., J. Control ReL, 1990, 14, 43-51). [00100] Non-chelating non-surfactants: As used herein, nonchelating non-surfactant penetration enhancing compounds can be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absoφtion of oligonucleotides through the alimentary mucosa (Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33). This class of penetration enhancers include, for example, unsaturated cyclic ureas, 1 -alkyl- and 1- alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and non-steroidal anti- inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al., J. Pharm. Pharmacol, 1987, 39, 621- 626).

[00101] Agents that enhance uptake of oligonucleotides at the cellular level may also be added to the pharmaceutical and other compositions ofthe present invention. For example, cationic lipids, such as lipofectin (Junichi et al, U.S. Patent No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), are also known to enhance the cellular uptake of oligonucleotides.

[00102] Other agents may be utilized to enhance the penetration ofthe administered nucleic acids, including glycols such as ethylene glycol and propylene glycol, pyrrols such as 2-pyrrol, azones, and teφenes such as limonene and menthone.

[00103] Carriers

[00104] Certain compositions ofthe present invention also incoφorate carrier compounds in the formulation. As used herein, "carrier compound" or "carrier" can refer to a nucleic acid, or analog thereof, which is inert (i.e., does not possess biological activity per se) but is recognized as a nucleic acid by in vivo processes that reduce the bioavailability of a nucleic acid having biological activity by, for example, degrading the biologically active nucleic acid or promoting its removal from circulation. The coadministration of a nucleic acid and a carrier compound, typically with an excess ofthe latter substance, can result in a substantial reduction ofthe amount of nucleic acid recovered in the liver, kidney or other extracirculatory reservoirs, presumably due to competition between the carrier compound and the nucleic acid for a common receptor. For example, the recovery of a partially phosphorothioate oligonuclectide in hepatic tissue can be reduced when it is coadministered with polyinosinic acid, dextran sulfate, polycytidic acid or 4-acetamido-4'isothiocyano-stilbene- 2,2'disulfonic acid (Miyao et al., Antisense Res. Dev., 1995, 5, 115-121; Takakura et al., Antisense & Nucl. Acid Drug Dev., 1996, 6, 177- 183).

[00105] Excipients

[00106] In contrast to a canier compound, a "pharmaceutical carrier" or

"excipient" is a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal. The excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a nucleic acid and the other components of a given pharmaceutical composition. Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinized maize starch, polyvinylpynolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); and wetting agents (e.g., sodium lauryl sulphate, etc.). [00107] Pharmaceutically acceptable organic or inorganic excipient suitable for non-parenteral administration which do not deleteriously react with nucleic acids can also be used to formulate the, compositions ofthe present invention. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethy 1 cellulose, polyvinylpynolidone and the like. [00108] Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions ofthe nucleic acids in liquid or solid oil bases. The solutions may also contain buffers, diluents and other suitable additives. Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can be used.

[00109] Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethy 1 cellulose, polyvinylpynolidone and the like.

[00110] Other Components

[00111] The compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharrnaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms ofthe compositions ofthe present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities ofthe components ofthe compositions ofthe present invention.' The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) ofthe formulation. [00112] Aqueous suspensions may contain substances which increase the viscosity ofthe suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers. [00113] Certain embodiments ofthe invention provide pharmaceutical compositions containing (a) one or more antisense compounds and (b) one or more other chemotherapeutic agents which function by a non-antisense mechanism. Examples of such chemotherapeutic agents include, but are not limited to, anticancer drags such as daunorubicin, dactinomycin, doxorubicin, bleomycin, mitomycin, nitrogen mustard, chlorambucil, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine (CA), 5-fluorouracil (5-FU), floxuridine (5-FUdR), methofrexate (MTX), colchicine, vincristine, vinblastine, etoposide, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 1206- 1228). Anti-inflammatory drags, including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, may also be combined in compositions ofthe invention. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively), other non- antisense chemotherapeutic agents are also within the scope of this invention. Two or more combined compounds may be used together or sequentially. [00114] In another related embodiment, compositions ofthe invention may contain one or more antisense compounds, particularly oligonucleotides, targeted to a first nucleic acid and one or more additional antisense compounds targeted to a second nucleic acid target. Numerous examples of antisense compounds are known in the art. Two or more combined compounds may be used together or sequentially. [00115] The formulation of therapeutic compositions and their subsequent administration is believed to be within the skill of those in the art. Dosing is dependent on severity and responsiveness ofthe disease state to be treated, with the course of treatment lasting from several days to several months, or until a cure is effected or a diminution ofthe disease state is achieved. Optimal dosing schedules can be calculated from measurements of drug accumulation in the body ofthe patient. Persons of ordinary skill can easily determine optimum dosages, dosing methodologies and repetition rates. Optimum dosages may vary depending on the relative potency of individual oligonucleotides, and can generally be estimated based on EC₅₀s found to be effective in in vitro and in vivo animal models. In general, dosage is from 0.01 μg to 100 g per kg of body weight, and may be given once or more daily, weekly, monthly or yearly, or even once every 2 to 20 years. Persons of ordinary skill in the art can easily estimate repetition rates for dosing based on measured residence times and concentrations ofthe drug in bodily fluids or tissues. Following successful treatment, it may be desirable to have the patient undergo maintenance therapy to prevent the recunence ofthe disease state, wherein the oligonucleotide is administered in maintenance doses, ranging from 0.01 μg to 100 g per kg of body weight, once or more daily, to once every 20 years. [00116] While the present invention has been described with specificity in accordance with certain of its prefened embodiments, the following examples serve only to illustrate the invention and are not intended to limit the same.

EXAMPLES

Example 1

Nucleoside Phosphoramidites for Oligonucleotide Synthesis Deoxy and

2'-alkoxy amidites [00117] 2'-Deoxy and 2'-methoxy beta-cyanoethyldiisopropyl phosphoramidites are available from commercial sources (e.g. Chemgenes, Needham MA or Glen Research, Inc. Sterling VA). Other 2'-O-alkoxy substituted nucleoside amidites are prepared as described in U.S. Patent 5,506,351 , herein incoφorated by reference. For oligonucleotides synthesized using 2 '-alkoxy amidites, the standard cycle for unmodified oligonucleotides is utilized, except the wait step after pulse delivery of tetrazole and base is increased to 360 seconds. [00118] Oligonucleotides containing 5-methyl-2'-deoxycytidine (5-Me- C) nucleotides are synthesized according to published methods [Sanghvi, et. al., Nucleic Acids Research, 1993, 21, 3197-3203] using commercially available phosphoramidites (Glen Research, Sterling VA or ChemGenes, Needham MA). 2 '-Fluoro amidites 2'-Fluorodeoxyadenosine amidites

[00119] 2 '-fluoro oligonucleotides are synthesized as described previously [Kawasaki, et. al., J. Med. Chem., 1993, 36, 831-841] and United States patent 5,670,633, herein incoφorated by reference. Briefly, the protected nucleoside N6-benzoyl-2'-deoxy-2'-fluoroadenosine is synthesized utilizing commercially available 9-beta-D- arabinofuranosyladenine as starting material and by modifying literature procedures whereby the 2'-alpha-fluoro atom is introduced by a SN2- displacement of a 2'-beta-trityl group. Thus N6-benzoyl-9-beta-D- arabinofuranosyladenine is selectively protected in moderate yield as the 3',5'-ditetrahydropyranyl (THP) intermediate. Deprotection ofthe THP and N6-benzoyl groups is accomplished using standard methodologies and standard methods are used to obtain the 5'-dimethoxytrityl-(DMT) and 5'- DMT-3 '-phosphoramidite intermediates. 2 '-Fluorodeoxyguanosine [00120] The synthesis of 2'-deoxy-2'-fluoroguanosine is accomplished using tetraisopropyldisiloxanyl (TPDS) protected 9-beta-D- arabinofuranosylguanine as starting material, and conversion to the intermediate diisobutyrylarabinofuranosylguanosine. Deprotection ofthe TPDS group is followed by protection ofthe hydroxyl group with THP to give diisobutyryl di-THP protected arabinofuranosylguanine. Selective O- deacylation and inflation is followed by treatment ofthe crude product with fluoride, then deprotection ofthe THP groups. Standard methodologies are used to obtain the 5'-DMT- and 5 '-DMT-3 '-phosphoramidites. 2 '-Fluorouridine [00121] Synthesis of 2 '-deoxy-2 '-fluorouridine is accomplished by the modification of a literature procedure in which 2,2'anhydro-l-beta-D- arabinofuranosyluracil is treated with 70% hydrogen fluoride-pyridine. Standard procedures are used to obtain the 5' -DMT and 5'-DMT-3'- phosphoramidites. 2'-Fluorodeoxycytidine

[00122] 2' -deoxy-2 '-fluorocytidine is synthesized via amination of 2'- deoxy-2' -fluorouridine, followed by selective protection to give N4- benzoyl-2' -deoxy-2 '-fluorocytidine. Standard procedures are used to obtain the 5'-DMT and 5 '-DMT-3 'phosphoramidites. 2'-O-(2-Methoxyethyl) modified amidites [00123] 2 '-O-Methoxy ethyl-substituted nucleoside amidites are prepared as follows, or alternatively, as per the methods of Martin, P., Helvetica Chimica Acta, 1995, 78, 486-504.

2,2'-Anhydro[l-(beta-D-arabinofuranosyl)-5-methyluridinel [00124] 5-Methyluridine (ribosylthymine, commercially available through Yamasa, Choshi, Japan) (72.0 g, 0.279 M),, diphenylcarbonate (90.0 g, 0.420 M) and sodium bicarbonate (2.0 g, 0.024 M) are added to DMF (300 mL). The mixture is heated to reflux, with stirring, allowing the evolved carbon dioxide gas to be released in a controlled manner. After 1 hour, the slightly darkened solution is concentrated under reduced pressure. The resulting syrup is poured into diethylether (2.5 L), with stirring. The product formed a gum. The ether is decanted and the residue is dissolved in a minimum amount of methanol (ca. 400 mL). The solution is poured into fresh ether (2.5 L) to yield a stiff gum. The ether is decanted and the gum is dried in a vacuum oven (60°C at 1 mm Hg for 24 h) to give a solid that is crushed to a light tan powder. The material is used as is for further reactions (or it can be purified further by column chromatography using a gradient of methanol in ethyl acetate (10-25%) to give a white solid. 2'-O-Methoxyethyl-5-methyluridine [00125] 2,2'-Anhydro-5-methyluridine (195 g, 0.81 M), tris(2- methoxyethyl)borate (231 g, 0.98 M) and 2-methoxyethanol (1.2 L) are added to a 2 L stainless steel pressure vessel and placed in a pre-heated oil bath at 160°C. After heating for 48 hours at 155-160°C, the vessel is opened and the solution evaporated to dryness and triturated with MeOH (200 mL). The residue is suspended in hot acetone (1 L). The insoluble salts are filtered, washed with acetone (150 mL) and the filtrate evaporated. The residue (280 g) is dissolved in CH₃CN (600 mL) and evaporated. A silica gel column (3 kg) is packed in CH₂CI₂ /acetone /MeOH (20:5:3) containing_^ 0.5% Et₃NH. The residue is dissolved in CH2CI2 (250 mL) and adsorbed onto silica (150 g) prior to loading onto the column. The product is eluted with the packing solvent to give the title product. Additional material can be obtained by reworking impure fractions. 2'-O-Methoxyethyl-5'-O-dimethoxytrityl-5-methyluridine [00126] 2'-O-Methoxyethyl-5-methyluridine (160 g, 0.506 M) is co- evaporated with pyridine (250 mL) and the dried residue dissolved in pyridine (1.3 L). A first aliquot of dimethoxytrityl chloride (94.3 g, 0.278 M) is added and the mixture stined at room temperature for one hour. A second aliquot of dimethoxytrityl chloride (94.3 g, 0.278 M) is added and the reaction stined for an additional one hour. Methanol (170 mL) is then added to stop the reaction. The solvent is evaporated and triturated with CH₃CN (200 mL) The residue is dissolved in CHC1 (1.5 L) and extracted with 2x500 mL of saturated NaHCO₃ and 2x500 mL of saturated NaCl. The organic phase is dried over Na₂SO₄, filtered, and evaporated. The residue is purified on a 3.5 kg silica gel column, packed and eluted with EtOAc/hexane/ acetone (5:5:1) containing 0-5%> Et₃NH. The pure fractions are evaporated to give the title product.

3'-O-Acetyl-2'-O-methoxyethyl-5'-O-dimethoxytrityl-5-methyluridine [00127] 2'-O-Methoxyethyl-5'-O-dimethoxytrityl-5-methyluridine (106 g, 0.167 M), DMF/pyridine (750 mL of a 3:1 mixture prepared from 562 mL of DMF and 188 mL of pyridine) and acetic anhydride (24.38 mL, 0.258 M) are combined and stined at room temperature for 24 hours. The reaction is monitored by TLC by first quenching the TLC sample with the addition of MeOH. Upon completion ofthe reaction, as judged by TLC, MeOH (50 mL) is added and the mixture evaporated at 35°C. The residue is dissolved in CHC 1₃ (800 mL) and extracted with 2x200 mL of saturated sodium bicarbonate and 2x200 mL of saturated NaCl. The water layers are back extracted with 200 mL of CHC1₃. The combined organics are dried with sodium sulfate and evaporated to a residue. The residue is purified on a 3.5 kg silica gel column and eluted using EtOAc/hexane(4:l). Pure product fractions are evaporated to yield the title compounds.

3'-O-Acetyl-2'-O-methoxyethyl-5'-O-dimethoxytrityl-5-methyl-4- triazoleuridine

[00128] A first solution is prepared by dissolving 3'-O-acetyl-2'-O- methoxyethyl-5'-O-dimethoxytrityl-5-methyluridine (96 g, 0.144 M) in CH₃CN (700 mL) and set aside. Triethylamme (189 mL, 1.44 M) is added to a solution of triazole (90 g, 1.3 M) in CH₃CN (1 L), cooled to -5°C and stined for 0.5 h using an overhead stiner. POCl₃ is added dropwise, over a 30 minute period, to the stined solution maintained at 0-10°C, and the resulting mixture stined for an additional 2 hours. The first solution is added dropwise, over a 45 minute period, to the latter solution. The resulting reaction mixture is stored overnight in a cold room. Salts are filtered from the reaction mixture and the solution is evaporated. The residue is dissolved in EtOAc (1 L) and the insoluble solids are removed by filtration. The filtrate is washed with 1x300 mL of NaHCO₃ and 2x300 mL of saturated NaCl, dried over sodium sulfate and evaporated. The residue is triturated with EtOAc to give the title compound. 2'-O-Methoxyethyl-5'-O-dimethoxytrityl-5-methylcytidine [00129] A solution of 3 '-O-acetyl-2'-O-methoxyethyl-5'-O- dimethoxytrityl-5-methyl-4-triazoleuridine (103 g, 0.141 M) in dioxane (500 mL) and NH₄OH (30 mL) is stined at room temperature for 2 hours. The dioxane solution is evaporated and the residue azeotroped with MeOH (2x200 mL). The residue is dissolved in MeOH (300 mL) and transfened to a 2 liter stainless steel pressure vessel. MeOH (400 mL) saturated with NH₃ gas is added and the vessel heated to 100°C for 2 hours (TLC showed complete conversion). The vessel contents are evaporated to dryness and the residue is dissolved in EtOAc (500 mL) and washed once with saturated NaCl (200 mL). The organics are dried over sodium sulfate and the solvent is evaporated to give the title compound. N4-Benzoyl-2'-O-methoxyethyl-5'-O-dimethoxytrityl- 5-methylcytidine

[00130] 2 '-O-Methoxyethyl-5 '-O-dimethoxytrityl-5-methylcytidine (85 g, 0.134 M) is dissolved in DMF (800 mL) and benzoic anhydride (37.2 g, 0.165 M) is added with stining. After stirring for 3 hours, TLC showed the reaction to be approximately 95%> complete. The solvent-'is evaporated and the residue azeotroped with MeOH (200 mL). The residue is dissolved in CHC1₃ (700 mL) and extracted with saturated NaHCO, (2x300 mL) and saturated NaCl (2x300 mL) , dried over MgSO₄ and evaporated to give a residue. The residue is chromatographed on a 1.5 kg silica column using EtOAc/hexane (1:1) containing 0-5% Et₃NH as the eluting solvent. The pure product fractions are evaporated to give the title compound. N4-Benzoyl-2'-O-methoxyethyl-5'-O-dimethoxytrityI-5-methykytidine- 3'-amidite [00131] N4-Benzoyl-2'-O-methoxyethyl-5'-O-dimethoxytrityl-5- methylcytidine (74 g, 0.10 M) is dissolved in CH₂C1₂ (1 L) Tetrazole diisopropylamine (7.1 g) and 2-cyanoethoxy-tetra(isopropyl)phosphite (40.5 mL, 0.123 M) are added with stining, under a nitrogen atmosphere. The resulting mixture is stined for 20 hours at room temperature (TLC showed the reaction to be 95% complete). The reaction mixture is extracted with saturated NaHCO₃ (1x300 mL) and saturated NaCl (3x300 mL). The aqueous washes are back-extracted with CH2CI₂ (300 mL), and the extracts are combined, dried over MgSO₄ and concentrated. The residue obtained is chromatographed on a 1.5 kg silica column using EtOAc/hexane (3:1) as the eluting solvent. The pure fractions were combined to give the title compound.

2'-O-(Aminooxyethyl) nucleoside amidites and 2'-O- (dimethylaminooxyethyl) nucleoside amidites 2'-(Dimethylaminooxyethoxy) nucleoside amidites [00132] 2 '-(Dimethylaminooxy ethoxy) nucleoside amidites [also known in the art as 2'-O-(dimethylaminooxyethyl) nucleoside amidites] are prepared as described in the following paragraphs. Adenosine, cytidine and guanosine nucleoside amidites are prepared similarly to the thymidine (5- methyluridine) except the exocyclic amines are protected with a benzoyl moiety in the case of adenosine and cytidine and with isobutyryl in the case of guanosine.

5'-O-tert-Butyldiphenylsilyl -O² -2'-anhydro-5-methyluridine

[00133] O² -2'-anhydro-5-methyluridine (Pro. Bio. Sint, Varese, Italy, 1 OO.Og, 0.4'6 mmol), dimethylaminopyridine (0.66g, 0.013eq, 0.0054mmol) are dissolved in dry pyridine (500 ml) at ambient temperature under an argon atmosphere and with mechanical stirring, tert- Butyldiphenylchlorosilane (125.8g, 119.0mL, l.leq, 0.458mmol) is added in one portion. The reaction is stined for 16 h at ambient temperature. TLC (Rf 0.22, ethyl acetate) indicated a complete reaction. The solution is concentrated under reduced pressure to a thick oil. This is partitioned between dichloromethane (1 L) and saturated sodium bicarbonate (2x1 L) and brine (1 L). The organic layer is dried over sodium sulfate and concentrated under reduced pressure to a thick oil. The oil is dissolved in a 1:1 mixture of ethyl acetate and ethyl ether (600mL) and the solution is cooled to -10°C. The resulting crystalline product is collected by filtration, washed with ethyl ether (3x200 mL), and dried (40°C, 1mm Hg, 24 h) to a white solid 5'-O-tert-Butyldiphenylsilyl-2'-O-(2-hydroxyethyl)-5-methyluridine [00134] In a 2 L stainless steel, unstined pressure reactor is added borane in tetrahydrofuran (1.0 M, 2.0 eq, 622 mL). In the fume hood and with manual stining, ethylene glycol (350 mL, excess) is added cautiously at first until the evolution of hydrogen gas subsides. 5'-O-tert-Butyldiphenylsilyl- O -2'anhydro-5-methyluridine (149 g, 0.3' 1 mol) and sodium bicarbonate (0.074 g, 0.003 eq) are added with manual stirring. The reactor is sealed and heated in an oil bath until an internal temperature of 160°C is reached and then maintained for 16 h (pressure < 100 psig). The reaction vessel is cooled to ambient and opened. TLC (Rf 0.67 for desired product and Rf 0.82 for ara-T side product, ethyl acetate) indicated about 70%> conversion to the product. In order to avoid additional side product formation, the reaction is stopped, concentrated under reduced pressure (10 to 1mm, Hg) in a warm water bath (40-100°C) with the more extreme conditions used to remove the ethylene glycol. [Alternatively, once the low boiling solvent is gone, the remaining solution can be partitioned between ethyl acetate and water. The product will be in the organic phase.] The residue is purified by column chromatography (2kg silica gel, ethyl acetate-hexanes gradient 1 :1 to 4:1). The appropriate fractions are combined, stripped and dried to product as a white crisp foam, contaminated starting material, and pure reusable starting material. 2'-O-([2-phthalimidoxy)ethyl]-5'-t-butyldiphenylsilyl-5-methyluridine [00135] 5 '-O-tert-Butyldiphenylsilyl-2'-O-(2-hydroxyethyl)-5- methyluridine (20g, 36.98mmol) is mixed with triphenylphosphine (11.63g, 44.36mmol) and N-hydroxyphthalimide (7.24g, 44.36mmol). It is then dried over P₂O₅ under high vacuum for two days at 40°C. The reaction mixture is flushed with argon and dry THF (369.8mL, Aldrich, sure seal bottle) is added to get a clear solution. Diethyl-azodicarboxylate (6.98mL, ' 44.36mmol) is added dropwise to the reaction mixture. The rate of addition is maintained such that resulting deep red coloration is just discharged before adding the next drop. After the addition is complete, the reaction is stined for 4 hrs. By that time TLC showed the completion of the reaction (ethylacetate:hexane, 60:40). The solvent is evaporated in vacuum. Residue obtained is placed on a flash column and eluted with ethyl acetate :hexane (60:40), to get 2'-O-([2-phthalimidoxy)ethyl]-5'-t-butyldiphenylsilyl-5- methyluridine as white foam. 5'-O-tert-butyIdiphenylsiIyl-2'-O-[(2-formadoximinooxy)ethyl]-5- methyluridine

[00136] 2 '-O-([2-phthalimidoxy)ethyl]-5 '-t-butyldiphenylsilyl-5- methyluridine (3.1g, 4.5mmol) is dissolved in dry CH₂CI₂ (4.5mL) and methylhydrazine (300mL, 4.64mmol) is added dropwise at -10°C to O°C. After 1 h the mixture is filtered, the filtrate is washed with ice cold CH₂CI₂ and the combined organic phase is washed with water, brine and dried over anhydrous Na₂SO₄. The solution is concentrated to get 2'-O(aminooxyethyl) thymidine, which is then dissolved in MeOH (67.5mL). To this formaldehyde (20%> aqueous solution, w/w, 1.1 eq.) is added and the resulting mixture is strined for 1 h. Solvent is removed under vacuum; residue chromatographed to get 5'-O-tert-butyldiphenylsilyl-2'-O-[(2- formadoximinooxy) ethyl]-5-methyluridine as white foam. 5'-O-tert-Butyldiphenylsilyl-2'-O-[N,N-dimethylaminooxyethyl]-5- methyluridine [00137] 5'-O-tert-butyldiphenylsilyl-2'-O-[(2- fonnadoximinooxy)ethyl]- 5-methyluridine (1.77g, 3.12mmol) is dissolved in a solution of IM pyridinium p-toluenesulfonate (PPTS) in dry MeOH (30.6mL). Sodium cyanoborohydride (0.39g, 6.13mmol) is added to this solution at 10°C under inert atmosphere. The reaction mixture is stined for 10 minutes at 10°C. After that the reaction vessel is removed from the ice bath and stined at room temperature for 2 h, the reaction monitored by TLC (5%> MeOH in CH₂CI₂). Aqueous NaHCO₃ solution (5%, lOmL) is added and extracted with ethyl acetate (2x20mL). Ethyl acetate phase is dried over anhydrous Na₂SO₄, evaporated to dryness. Residue is dissolved in a solution of IM PPTS in MeOH (30.6mL). Formaldehyde (20% w/w, 30mL, 3.37mmol) is added and the reaction mixture is stined at room temperature for 10 minutes. Reaction mixture cooled to 10°C in an ice bath, sodium cyanoborohydride (0.39g, 6.13mmol) is added, and reaction mixture stined at 10°C for 10 minutes. After 10 minutes, the reaction mixture is removed from the ice bath and stined at room temperature for 2 hrs. To the reaction mixture 5%> NaHCO₃ (25mL) solution is added and extracted with ethyl acetate (2x25mL). Ethyl acetate layer is dried over anhydrous Na₂SO₄ and evaporated to dryness. The residue obtained is purified by flash column chromatography and eluted with 5%> MeOH in CH₂C1₂ to get 5'-O- tertbutyldiphenylsilyl-2'-O-[N,N-dimethylaminooxyethyl]-5- methyluridine as a white foam.

2'-O-(dimethylaminooxyethyl)-5-methyIuridine

[00138] Triethylamme trihydrofluoride (3.91mL, 24.0mmol) is dissolved in dry THF and triethylamme (1.67mL, 12mmol, dry, kept over KOH). This mixture of triethylamine-2HF is then added to 5'-O-tert-butyldiphenylsilyl- 2'-O-[N,N-dhnethylaminooxyethyl]-5-methyluridine (1.40g, 2.4mmoi) and stined at room temperature for 24 hrs. Reaction is monitored by TLC (5% MeOH in CH₂C1₂). Solvent is removed under vacuum and the residue placed on a flash column and eluted with 10% MeOH in CH₂C1₂ to get 2'-O- (dimethylaminooxyethyl)-5-methyluridine. 5'-O-DMT-2'-O-(dimethylaminooxyethyl)-5-methyluridine [00139] 2'-O-(dimethylaminooxyethyl)-5-methyluridine (750mg, 2.17mmol) is dried over P₂O₅ under high vacuum overnight at 40°C. It is then co-evaporated with anhydrous pyridine (20mL). The residue obtained is dissolved in pyridine (1 lmL) under argon atmosphere. 4- dimethylaminopyridine (26.5mg, 2.60mmol), 4,4 '-dimethoxytrityl chloride (880mg, 2.60mmol) is added to the mixture and the reaction mixture is stined at room temperature until all ofthe starting material disappeared. Pyridine is removed under vacuum and the residue chromatographed and eluted with 10%> MeOH in CH₂C1₂ (containing a few drops of pyridine) to get 5 '-O-DMT-2'-0(dimethylamino-oxyethyl)-5-methyluridine. 5'-O-DMT-2'-O-(2-N,N-dimethylammooxyethyl)-5-methyluridine-3'- [(2-cyanoethyl)-N,N- diisopropylphosphoramidite] [00140] 5 '-O-DMT-2'-O-(dimethylaminooxyethyl)-5-methyluridine (l.OSg, 1.67mmol) is co-evaporated with toluene (20mL). To the residue N,N-diisopropylamine tetrazonide (0.29g, 1.67mmol) is added and dried over P20, under high vacuum overnight at 40°C. Then the reaction mixture is dissolved in anhydrous acetonitrile (8.4mL) and 2-cyanoethyl-N,N,N -N¹- tetraisopropylphosphoramidite (2.12mL, 6.08mmol) is added. The reaction mixture is stined at ambient temperature for 4 hrs under inert atmosphere. The progress ofthe reaction is monitored by TLC (hexane:ethyl acetate 1 :1). The solvent is evaporated, then the residue is dissolved in ethyl acetate (70mL) and washed with 5%o aqueous NaHC0₃ (40mL). Ethyl acetate layer is dried over anhydrous Na₂SO₄ and concentrated. Residue obtained is chromatographed (ethyl acetate as eluent) to get 5 '-O-DMT-2'-O-(2-N,N- dimethylaminooxyethyl)-5-methyluridine-3'-[(2-cyanoethyl)-N,N- diisopropylphosphoramidite] as a foam. 2'-(Aminooxyethoxy) nucleoside amidites

[00141] 2 '-(Aminooxy ethoxy) nucleoside amidites [also known in the art as 2'-O-(aminooxyethyl) nucleoside amidites] are prepared as described in the following paragraphs. Adenosine, cytidine and thymidine nucleoside amidites are prepared similarly.

N2-isobutyryl-6-O-diphenylcarbamoyl-2'-O-(2-ethylacetyl)-5'-O-(4,4'- dimethoxytrityI)guanosine-3'-[(2-cyanoethyl)-N,N- diisopropylphosphoramidite]

[00142] The 2'-O-aminooxyethyl guanosine analog may be obtained by selective 2'-O-alkylation of diaminopurine riboside. Multigram quantities of diaminopurine riboside may be purchased from Schering AG (Berlin) to provide 2'-O-(2-ethylacetyl) diaminopurine riboside along with a minor amount ofthe 3'-O-isomer. 2'-0-(2-ethylacetyl) diaminopurine riboside may be resolved and converted to 2'-O-(2ethylacetyl)guanosine by treatment with adenosine deaminase. (McGee, D. P. C, Cook, P. D., Guinosso, C. J., WO 94/02501 Al 940203.) Standard protection procedures should afford 2'-O-(2-ethylacetyl)-5'-O-(4,4'-dimethoxytrityl)guanosine and 2-N-isobutyryl-6-O-diphenylcarbamoyl-2'-O-(2-ethylacetyl)-5 '-O- (4,4'-dimethoxytrityl)guanosine which may be reduced to provide 2-N- isobutyryl-6-O-diphenylcarbamoyl-2 ' -O-(2-ethylacetyl)-5 ' -O-(4,4 '- dimethoxytrityl)guanosine. As before the hydroxyl group may be displaced by N-hydroxyphthalimide via a Mitsunobu reaction, and the protected nucleoside may phosphitylated as usual to yield 2-N-isobutyryl-6-O- diphenylcarbamoyl-2 ' -O-(2-ethylacetyl)-5 ' -O-(4,4 '- dimethoxytrityl)guanosine-3'-[(2-cyanoethyl)-N,N- diisopropylphosphoramiditel .

2 '-dimethylaminoethox ethoxy (2'-DMAEOE) nucleoside amidites [00143] 2 '-dimethylaminoethoxy ethoxy nucleoside amidites (also known in the art as 2'-O-dimethylaminoethoxyethyl, i.e., 2O-CH₂-O-CH₂- N(CH₂)₂, or 2'-DMAEOE nucleoside amidites) are prepared as follows. Other nucleoside amidites are prepared similarly. 2'-O-[2(2-N,N-dimethylaminoethoxy)ethyl]-5-methyl uridine [00144] 2[2-(Dimethylamino)ethoxylethanol (Aldrich, 6.66 g, 50 mmol) is slowly added to a solution of borane in tetrahydrofuran (1 M, 10 mL, 10 mmol) with stirring in a 100 mL bomb. Hydrogen gas evolves as the solid dissolves. O²-, 2' - anhydro-5-methyluridine (1.2 g, 5 mmol), and sodium bicarbonate (2.5 mg) are added and the bomb is sealed, plaped in an oil bath and heated to 155°C for 26 hours. The bomb is cooled to room temperature and opened. The crude solution is concentrated and the residue partitioned between water (200 mL) and hexanes (200 mL). The excess phenol is extracted into the hexane layer. The aqueous layer is extracted with ethyl acetate (3x200 mL) and the combined organic layers are washed once with water, dried over anhydrous sodium sulfate and concentrated. The residue is columned on silica gel using methanol/methylene chloride 1 :20 (which has 2%o triethylamme) as the eluent. As the column fractions are concentrated a colorless solid forms which is collected to give the title compound as a white solid. 5'-O-dimethoxytrityl-2'-O-[2(2-N,N-dimethylaminoethoxy) ethyl)]-5- methyl uridine

[00145] To 0.5 g (1.3 mmol) of 2'-O-[2(2-N,N- dimethylaminoethoxy)ethyl) 1-5 -methyl uridine in anhydrous pyridine (8 mL), triethylamine (0.36 mL) and dimethoxytrityl chloride (DMT-Cl, 0.87 g, 2 eq.) are added and stined for 1 hour. The reaction mixture is poured into water (200 mL) and extracted with CH₂CI₂ (2x200 mL). The combined CH₂CI₂ layers are washed with saturated NaHCO₃ solution, followed by saturated NaCl solution and dried over anhydrous sodium sulfate. Evaporation of the solvent followed by silica gel chromatography using MeOH: CH₂Cl₂:Et₃N (20:1, v/v, with 1% triethylamine) gives the title compound.

5'-O-Dimethoxytrityl-2'-O-[2(2-N,N-dimethylaminoethoxy)ethyl)]-5- methyl uridine-3'-O-(cyanoethyl-N,N-diisopropyI)phosphoramidite [00146] Diisopropylammotetrazolide (0.6 g) and 2-cyanoethoxyN,N- diisopropyl phosphoramidite (1.1 mL, 2 eq.) are added to a solution of 5'-O- dimethoxytrityl-2'-O-[2(2-N,N-dimethylaminoethoxy)ethyl)]-5- methyluridine (2.17 g, 3 mmol) dissolved in CH₂C1₂ (20 mL) under an atmosphere of argon. The reaction mixture is stined overnight and the solvent evaporated. The resulting residue is purified by silica gel flash column chromatography with ethyl acetate as the eluent to give the title compound.

Example 2 Oligonucleotide synthesis [00147] Unsubstituted and substituted phosphodiester (P=O) oligonucleotides are synthesized on an automated DNA synthesizer (Applied Biosystems model 380B) using standard phosphoramidite chemistry with oxidation by iodine. [00148] Phosphorothioates (P=S) are synthesized as for the phosphodiester oligonucleotides except the standard oxidation bottle is replaced by 0.2 M solution of 3H-l,2-benzodithiole-3-one 1,1-dioxide in acetonitrile for the stepwise thiation ofthe phosphite linkages. The thiation wait step is increased to 68 sec and is followed by the capping step. After cleavage from the CPG column and deblocking in concentrated ammonium hydroxide at 55°C (18 h), the oligonucleotides are purified by precipitating twice with 2.5 volumes of ethanol from a 0.5 M NaCl solution. Phosphinate oligonucleotides are prepared as described in U.S. Patent 5,508,270, herein incoφorated by reference. [00149] Alkyl phosphonate oligonucleotides are prepared as described in U.S. Patent 4,469,863, herein incoφorated by reference. [00150] 3 '-Deoxy-3 '-methylene phosphonate oligonucleotides are prepared as described in U.S. Patents 5,610,289 or 5,625,050, herein incoφorated by reference. [00151] Phosphoramidite oligonucleotides are prepared as described in U.S. Patent, 5,256,775 or U.S. Patent 5,366,878, herein incoφorated by reference.

[00152] Alkylphosphonothioate oligonucleotides are prepared as described in WO 94/17093 and WO 94/02499 herein incoφorated by reference. [00153] 3 '-Deoxy-3 '-amino phosphoramidate oligonucleotides are prepared as described in U.S. Patent 5,476,925, herein incoφorated by reference.

[00154] Phosphotriester oligonucleotides are prepared as described in U.S. Patent 5,023,243, herein incoφorated by reference.

[00155] Borano phosphate oligonucleotides are prepared as described in U.S. Patents 5,130,302 and 5,177,198, both herein incoφorated by reference.

Example 3

Oligonucleoside Synthesis

[00156] Methylenemethylimino linked oligonucleosides, also identified as MMI linked oligonucleosides, methylenedimethylhydrazo linked oligonucleosides, also identified as MDH linked oligonucleosides, and methylenecarbonylammo linked oligonucleosides, also identified as amide-3 linked oligonucleosides, and methyleneaminocarbonyl linked oligonucleosides, also identified as amide-4 linked oligonucleosides, as well as mixed backbone compounds having, for instance, alternating MMI and P=O or P^S linkages are prepared as described in U.S. Patents 5,378,825; 5,386,023; 5,489,677; 5,602,240; and 5,610,289, all of which are herein incoφorated by reference.

[00157] Formacetal and thioformacetal linked oligonucleosides are prepared as described in U.S. Patents 5,264,562 and 5,264,564, herein incoφorated by reference. [00158] Ethylene oxide linked oligonucleosides are prepared as described in U.S. Patent 5,223,618, herein incoφorated by reference.

Example 4 PNA Synthesis

[00159] Peptide nucleic acids (PNAs) are prepared in accordance with any ofthe various procedures refened to in Peptide Nucleic Acids (PNA): Synthesis, Properties and Potential Applications, Bioorganic & Medicinal Chemistry, 1996, 4, 523. They may also be prepared in accordance with U.S. Patents 5,539,082; 5,700,922; and 5,719,262, herein incoφorated by reference.

Example 5

Synthesis of Chimeric Oligonucleotides [00160] Chimeric oligonucleotides, oligonucleosides or mixed oligonucleotides/oligonucleosides ofthe invention can be of several different types. These include a first type wherein the "gap" segment of linked nucleosides is positioned between 5' and 3' "wing" segments of linked nucleosides and a second "open end" type wherein the "gap" segment is located at either the 3' or the 5' terminus ofthe oligomeric compound. Oligonucleotides ofthe first type are also known in the art as "gapmers" or gapped oligonucleotides. Oligonucleotides ofthe second type are also known in the art as "hemimers" or "wingmers". [2'-O-Me]~[2'-deoxy]~[2'-O-Me] Chimeric Phosphorothioate Oligonucleotides [00161] Chimeric oligonucleotides having 2'-O-alkyl phosphorothioate and 2'-deoxy phosphorothioate oligonucleotide segments are synthesized using an Applied Biosystems automated DNA synthesizer Model 380B, as above. Oligonucleotides are synthesized using the automated synthesizer and 2'-deoxy-5 '-dimethoxytrityl-3 '-O-phosphoramidite for the DNA portion and 5'-dimethoxytrityl-2'-O-methyl-3'-O-phosphoramidite for 5' and 3' wings. The standard synthesis cycle is modified by increasing the wait step after the delivery of tetrazole and base to 600 s repeated four times for RNA and twice for 2'-O-methyl. The fully protected oligonucleotide is cleaved from the support and the phosphate group is deprotected in 3 : 1 ammonia/ethanol at room temperature overnight then lyophilized to dryness. Treatment in methanolic ammonia for 24 hrs at room temperature is then done to deprotect all bases and sample is again lyophilized to dryness. The pellet is resuspended in IM TBAF in THF for 24 hrs at room temperature to deprotect the 2' positions. The reaction is then quenched with IM TEAA and the sample is then reduced to 1/2 volume by rotovac before being desalted on a G25 size exclusion column. The oligo recovered is then analyzed spectrophotometrically for yield and for purity by capillary electrophoresis and by mass spectrometry. [2'-O-(2-Methoxyethyl)]-[2'-deoxy]-[2'-O-(Methoxyethy])] Chimeric Phosphorothioate Oligonucleotides

[00162] [2'-O-(2-methoxyethyl)]-[2'-deoxy]— [-2'-O-(methoxyethyl)] chimeric phosphorothioate oligonucleotides are prepared as per the procedure above for the 2'-O-methyl chimeric oligonucleotide, with the substitution of phorothioate oligonucleotides are prepared as per the procedure abo 2'-O-(methoxyethyl) amidites for the 2'-O-methyl amidites. [2'-O-(2-Methoxyethyl)Phosphodiester]—[2'-deoxy Phosphorothioate]— [2'-O-(2-Methoxyethyι)] Phosphodiester] Chimeric Oligonucleotides [00163] [2'-O-(2-methoxyethyl phosphodiester]-[2'-deoxy phosphorothioate]~[2'-O-(methcixyethyl) phosphodiester] chimeric oligonucleotides are prepared as per the above procedure for the 2'-O- methyl chimeric oligonucleotide with the substitution of 2'-O- (methoxyethyl) amidites for the 2'-O-methyl amidites, oxidization with iodine to generate the phosphodiester internucleotide linkages within the wing portions ofthe chimeric structures and sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) to generate the phosphorothioate internucleotide linkages for the center gap. [00164] Other chimeric oligonucleotides, chimeric oligonucleosides and mixed chimeric oligonucleotides/oligonucleosides are synthesized according to United States patent 5,623,065, herein incoφorated by reference.

Example 6 Oligonucleotide Isolation [00165] After cleavage from the controlled pore glass column (Applied Biosystems) and deblocking in concentrated ammonium hydroxide at 55°C for 18 hours, the oligonucleotides or oligonucleosides are purified by precipitation twice out of 0.5 M NaCl with 2.5 volumes ethanol. Synthesized oligonucleotides are analyzed by polyacrylamide gel electrophoresis on denaturing gels and judged to be at least 85% full length material. The relative amounts of phosphorothioate and phosphodiester linkages obtained in synthesis are periodically checked by "P nuclear magnetic resonance spectroscopy, and for some studies oligonuclectides are purified by HPLC, as described by Chiang et al., J. Biol. Chem. 1991, 266, 18162-18171.

Example 7

Oligonucleotide Synthesis - 96 Well Plate Format

[00166] Oligonucleotides are synthesized via solid phase P(III) phosphoramidite chemistry on an automated synthesizer capable of assembling 96 sequences simultaneously in a standard 96 well format. Phosphodiester internucleotide linkages are afforded by oxidation with aqueous iodine. Phosphorothioate internucleotide linkages are generated by sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) in anhydrous acetonitrile. Standard base-protected beta- cyanoethyldiisopropyl phosphoramidites can be purchased from commercial vendors (e.g. PE- Applied Biosystems, Foster City, CA, or Pharmacia, Piscataway, NJ). Non-standard nucleosides are synthesized as per known literature or patented methods. They are utilized as base protected betacyanoethyldiisopropyl phosphoramidites.

[00167] Oligonucleotides are cleaved from support and deprotected with concentrated NH₄OH at elevated temperature (55-60°C) for 12-16 hours and the released product then dried in vacuo. The dried product is then resuspended in sterile water to afford a master plate from which all analytical and test plate samples are then diluted utilizing robotic pipettors. Example 8

Oligonucleotide Analysis - 96 Well Plate Format [00168] The concentration of oligonucleotide in each well is assessed by dilution of samples and UV absoφtion spectroscopy. The full-length integrity ofthe individual products is evaluated by capillary electrophoresis (CE) in either the 96 well format (Beckman P/ACE™ MDQ) or, for individually prepared samples, on a commercial CE apparatus (e.g., Beckman P/ACE™ 5000, ABI 270). Base and backbone composition is confirmed by mass analysis ofthe compounds utilizing electrospray-mass spectroscopy. All assay test plates are diluted from the master plate using single and multi-channel robotic pipettors. Plates are judged to be acceptable if at least 85% ofthe compounds on the plate are at least 85%> full length.

Example 9

Cell culture and oligonucleotide treatment

[00169] The effect of antisense compounds on target nucleic acid expression can be tested in any of a variety of cell types provided that the target nucleic acid is present at measurable levels. This can be routinely determined using, for example, PCR or Northern blot analysis. The following 6 cell types are provided for illustrative puφoses, but other cell types can be routinely used, provided that the target is expressed in the cell type chosen. This can be readily determined by methods routine in the art, for example Northern blot analysis, Ribonuclease protection assays, or RT- PCR.

T-24 cells:

[00170] The human transitional cell bladder carcinoma cell line T-24 is obtained from the American Type Culture Collection (ATCC) (Manassas, VA). T-24 cells are routinely cultured in complete McCoy's 5A basal media (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 10% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD), penicillin 100 units per mL, and streptomycin 100 micrograms per mL (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by trypsinization and dilution when they reached 90%> confluence. Cells are seeded into 96-well plates (Falcon-Primaria #3872) at a density of 7000 cells/well for use in RT-PCR analysis. [00171] For Northern blotting or other analysis, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide. A549 cells:

[00172] The human lung carcinoma cell line A549 can be obtained from the American Type Culture Collection (ATCC) (Manassas, VA). A549 cells are routinely cultured in DMEM basal media (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 10% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD), penicillin 100 units per mL, and streptomycin 100 micrograms per mL (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by trypsinization and dilution when they reached 90%> confluence. NHDF cells:

[00173] Human neonatal dermal fibroblast (NHDF) can be obtained from the Clonetics Coφoration (Walkersville MD). NHDFs are routinely maintained in Fibroblast Growth Medium (Clonetics Coφoration, Walkersville MD) supplemented as recommended by the supplier. Cells are maintained for up to 10 passages as recommended by the supplier. HEK cells:

[00174] Human embryonic keratinocytes (HEK) can be obtained from the Clonetics Coφoration (Walkersville MD). HEKs are routinely maintained in Keratinocyte Growth Medium (Clonetics Coφoration, Walkersville MD) formulated as recommended by the supplier. Cells are routinely maintained for up to 10 passages as recommended by the supplier. MCF-7 cells: [00175] The human breast carcinoma cell line MCF-7 is obtained from the American Type Culure Collection (Manassas, VA). MCF-7 cells are routinely cultured in DMEM low glucose (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 10% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by trypsinization and dilution when they reached 90% confluence. Cells are seeded into 96-well plates (Falcon-Primaria #3872) at a density of 7000 cells/well for use in RT-PCR analysis.

[00176] For Northern blotting or other analyses, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide. LA4 cells:

[00177] The mouse lung epithelial cell line LA4 is obtained from the American Type Culure Collection (Manassas, VA). LA4 cells are routinely cultured in F12K medium (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 15% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by, trypsinization and dilution when they reached 90% confluence. Cells are seeded into 96-well plates (Falcon-Primaria #3872) at a density of 3000-6000 cells/ well for use in RT-PCR analysis. [00178] For Northern blotting or other analyses, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide.

Treatment with antisense compounds: [00179] When cells reached 80% confluency, they are treated with oligonucleotide. For cells grown in 96-well plates, wells are washed once with 200 μL OPTI-MEM^tm-l reduced-serum medium (Gibco BRL) and then treated with 130 μL of OPTI-MEMTM™-l containing 3.75 μg/mL LIPOFECTIN™ (Gibco BRL) and the desired concentration of oligonucleotide. After 4-7 hours of treatment, the medium is replaced with fresh medium. Cells are harvested 16-24 hours after oligonucleotide treatment.

[00180] The concentration of oligonucleotide used varies from cell line to cell line. To determine the optimal oligonucleotide concentration for a particular cell line, the cells are treated with a positive control oligonucleotide at a range of concentrations.

Example 10 Analysis of oligonucleotide inhibition of LRHl expression

[00181] Antisense modulation of LRHl expression can be assayed in a variety of ways known in the art. For example, LRHl mRNA levels can be quantitated by, e.g., Northern blot analysis, competitive polymerase chain reaction (PCR), or real-time PCR (RT-PCR). Real-time quantitative PCR is presently prefened. RNA analysis can be performed on total cellular RNA or poly(A)+ mRNA. Methods of RNA isolation are taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 1, pp. 4.1.1-4.2.9 and 4.5.1-4.5.3, John Wiley & Sons, Inc., 1993. Northern blot analysis is routine in the art and is taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 1, pp. 4.2.1- 4.2.9, John Wiley & Sons, Inc., 1996. Real-time quantitative (PCR) can be conveniently accomplished using the commercially available ABI PRISM™ 7700 Sequence Detection System, available from PE-Applied Biosystems, Foster City, CA and used according to manufacturer's instructions. Prior to quantitative PCR analysis, primer-probe sets specific to the target gene being measured are evaluated for their ability to be "multiplexed" with a GAPDH amplification reaction. In multiplexing, both the target gene and the internal standard gene GAPDH are amplified concunenfly in a single sample. In this analysis, mRNA isolated from untreated cells is serially diluted. Each dilution is amplified in the presence of primer-probe sets specific for GAPDH only, target gene only ("single-plexing"), or both (multiplexing). Following PCR amplification, standard curves of GAPDH and target mRNA signal as a function of dilution are generated from both the single-plexed and multiplexed samples. If both the slope and conelation coefficient ofthe GAPDH and target signals generated from the multiplexed samples fall within 10% of their conesponding values generated from the single-plexed samples, the primer-probe set specific for that target is deemed as multiplexable. Other methods of PCR are also known in the art. [00182] Protein levels of LRH lean be quantitated in a variety of ways well known in the art, such as irmnunoprecipitation, Western blot analysis (immunoblotting), ELISA or fluorescence-activated cell sorting (FACS). Antibodies directed to LRH lean be identified and obtained from a variety of sources, such as the MSRS catalog of antibodies (Aerie Coφoration, Birmingham, MI), or can be prepared via conventional antibody generation methods. Methods for preparation of polyclonal antisera are taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.12.1-11.12.9, John Wiley & Sons, Inc., 1997. Preparation of monoclonal antibodies is taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.4.1 -11.11.5, John Wiley Sons, Inc., 1997.

[00183] Immunoprecipitation methods are standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 10.16.110.16.11, John Wiley & Sons, Inc., 1998. Western blot (immunoblot) analysis is standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 10.8.1-10.8.21, John Wiley Sons, Inc., 1997. Enzyme-linked immunosorbent assays (ELISA) are standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.2.1-11.2.22, John Wiley & Sons, Inc., 1991.

Example 11

Poly(A)+ mRNA isolation

[00184] Poly(A)+ mRNA is isolated according to Miura et al., Clin. Chem., 1996, 42, 1758-1764. Other methods for poly(A)+ mRNA isolation are taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 1, pp. 4.5.1-4.5.3, John Wiley & Sons, Inc., 1993. Briefly, for cells grown on 96-well plates, growth medium is removed from the cells and each well is washed with 200 μL cold PBS. 60 μL lysis buffer (10 mM Tris-HCl, pH 7.6, 1 mM EDTA, 0.5 M NaCl, 0.5% NP-40, 20 mM vanadyl-ribonucleoside complex) is added to each well, the plate is gently agitated and then incubated at room temperature for five minutes. 55 μL of lysate is transfened to Oligo d(T) coated 96-well plates (AGCT Inc., Irvine CA). Plates are incubated for 60 minutes at room temperature, washed 3 times with 200 μL of wash buffer (10 mM Tris-HCl pH 7.6, 1 mM EDTA, 0.3 M NaCl). After the final wash, the plate is blotted on paper towels to remove excess wash buffer and then air-dried for 5 minutes. 60 pL of elution buffer (5 mM Tris-HCl pH 7.6), preheated to 70°C is added to each well, the plate is incubated on a 90°C hot plate for 5 minutes, and the eluate is then transfened to a fresh 96-well plate. [00185] Cells grown on 100 mm or other standard plates may be treated similarly, using appropriate volumes of all solutions.

Example 12 Total RNA Isolation

[00186] Total mRNA is isolated using an RNEASY 96 kit and buffers purchased from Qiagen Inc. (Valencia CA) following the manufacturer's recommended procedures. Briefly, for cells grown on 96-well plates, growth medium is removed from the cells and each well is washed with 200 μL cold PBS. 100 μL Buffer RLT is added to each well and the plate vigorously agitated for 20 seconds. 100 μL of 70% ethanol is then added to each well and the contents mixed by pipetting three times up and down. The samples are then transfened to the RNEASY 96™ well plate attached to a QIAVAC™ manifold fitted with a waste collection tray and attached to a vacuum source. Vacuum is applied for 15 seconds. 1 mL of Buffer RWl is added to each well ofthe RNEASY 96™ plate and the vacuum again applied for 15 seconds. 1 mL of Buffer RPE is then added to each well ofthe RNEASY 96™ plate and the vacuum applied for a period of 15 seconds. The Buffer RPE wash is then repeated and the vacuum is applied for an additional 10 minutes. The plate is then removed from the QIAVAC^T manifold and blotted dry on paper towels. The plate is then re-attached to the QIAVAC manifold fitted with a collection tube rack containing 1.2 mL collection tubes. RNA is then eluted by pipetting 60 μL water into each well, incubating I minute, and then applying the vacuum for 30 seconds. The elution step is repeated with an additional 60 μL water. [00187] The repetitive pipetting and elution steps may be automated using a QIAGEN Bio-Robot 9604 (Qiagen, Inc., Valencia CA). Essentially, after lysing ofthe cells on the culture plate, the plate is transfened to the robot deck where the pipetting, DNase treatment and elution steps are carried out.

Example 13

Real-time Quantitative PCR Analysis of LRHlmRNA Levels

[00188] Quantitation of LRHlmRNA levels is determined by real-time quantitative PCR using the ABI PRISM™ 7700 Sequence Detection System (PE- Applied Biosystems, Foster City, CA) according to manufacturer's instructions. This is a closed-tube, non-gel-based, fluorescence detection system which allows high-throughput quantitation of polymerase chain reaction (PCR) products in real-time. As opposed to standard PCR, in which amplification products are quantitated after the PCR is completed, products in real-time quantitative PCR are quantitated as they accumulate. This is accomplished by including in the PCR reaction an oligonucleotide probe that anneals specifically between the forward and reverse PCR primers, and contains two fluorescent dyes. A reporter dye (e.g., JOE, FAM, or VIC, obtained from either Operon Technologies Inc., Alameda, CA or PE-

Applied Biosystems, Foster City, CA) is attached to the 5' end ofthe probe and a quencher dye (e.g., TAMRA, obtained from either Operon Technologies Inc., Alameda, CA or PE-Applied Biosystems, Foster City, CA) is attached to the 3 ' end ofthe probe. When the probe and dyes are intact, reporter dye emission is quenched by the proximity ofthe 3' quencher dye. During amplification, annealing ofthe probe to the target sequence creates a substrate that can be cleaved by the 5'-exonuclease activity of Taq polymerase. During the extension phase ofthe PCR amplification cycle, cleavage ofthe probe by Taq polymerase releases the reporter dye from the remainder ofthe probe (and hence from the quencher moiety) and a sequence-specific fluorescent signal is generated. With each cycle, additional reporter dye molecules are cleaved from their respective probes, and the fluorescence intensity is monitored at regular intervals by laser optics built into the ABI PRISM 7700 Sequence Detection System. In each assay, a series of parallel reactions containing serial dilutions of mRNA from untreated control samples generates a standard curve that is used to quantitate the percent inhibition after antisense oligonucleotide treatment of test samples. [00189] PCR reagents can be obtained from PE-Applied Biosystems, Foster City, CA. RT-PCR reactions are carried out by adding 25 μL PCR cocktail (lx TAQMAN^™ buffer A, 5.5 MM MgCl₂, 300 μM each of dATP, dCTP and dGTP, 600 μM of dUTP, 100 nM each of forward primer, reverse primer, and probe, 20 Units RNAse inhibitor, 1.25 Units AMPLITAQ GOLD^™, and 12.5 Units MuLV reverse transcriptase) to 96 well plates containing 25 μL poly(A) mRNA solution. The RT reaction is carried out by incubation for 30 minutes at 48°C. Following a 10 minute incubation at 95°C to activate the AMPLITAQ GOLD^™, 40 cycles of a two-step PCR protocol are carried out: 95 °C for 15 seconds (denaturation) followed by 60°C for 1.5 minutes (annealing/extension). [00190] Probes and primers to human LRHlwere designed to hybridize to a human LRHl sequence, using published sequence, information (GenBank accession number NM_003822, incoφorated herein as Figure 1. For human LRHl the PCR primers were: forward primer: LRH- 1 CCT GGT GCT CTT TAG TTT AGA TGT CAA SEQ ID NO : 3445 reverse primer: TCT GCT GCG GGT AGT TAC AC SEQ ID NO : 3446 A and the PCR probe is: FAM-AAT GCC GCC CTG CTG GAC TAC ACA SEQ ID NO : 3447 -BHl where FAM (PE- Applied Biosystems, Foster City, CA) is the fluorescent reporter dye) and BHl (PE- Applied Biosystems, Foster City, CA) is the quencher dye. For human cyclophilin the PCR primers were:

[00191] forward primer: CCCACCGTGTTCTTCGACAT SEQ ID NO : 3448 [00192] reverse primer: TTTCTGCTGTCTTTGGGACCTT SEQ ID NO : 3449 and the PCR probe is: 5' JOE-

CGCGTCTCCTTTGAGCTGTTTGCA SEQ ID NO : 3450 - TAMRA 3' where JOE (PE-Applied Biosystems, Foster City, CA) is the fluorescent reporter dye) and TAMRA (PE-Applied Biosystems, Foster City, CA) is the quencher dye.

Example 15

Antisense inhibition of human LRHlexpression by chimeric phosphorothioate oligonucleotides having 2'-MOE wings and a deoxy gap. [00193] In accordance with the present invention, a series of oligonucleotides are designed to target different regions ofthe human LRHl RNA, using published sequences (NM_003822 incoφorated herein as Figure 1). The oligonucleotides are shown in Table 1. "Target site" indicates the first (5 '-most) nucleotide number on the particular target sequence to which the oligonucleotide binds. The indicated parameters for each oligo was predicted using RNAstracture 3.7 by David H. Mathews, Michael Zuker and Douglas H. Turner. All compounds in Table 1 are chimeric oligonucleotides ("gapmers") 20 nucleotides in length, composed ^' of a central "gap" region consisting often 2'deoxynucleotides, which is flanked on both sides (5' and 3' directions) by four-nucleotide "wings". The wings are composed of 2 '-methoxyethyl (2'-MOE) nucleotides. The internucleoside (backbone) linkages are phosphorothioate (P=S) throughout the oligonucleotide. Cytidine residues in the 2'-MOE wings are 5- methylcytidines. All cytidine residues are 5-methylcytidine.

Table 1

kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CCGTTCTGTCCGTTTTTCTT

2171 SEQ ID NO: 1 -24.9 -26.8 75.8 -1.9 0 -2.6 ACCGTTCTGTCCGTTTTTCT

2172 SEQ ID NO: 2 -24.3 -26.9 76 -2.6 0 -2.6 GTGGGATGCTTGCTGGAGAG

1131 SEQ ID NO: 3 -24.1 -26.1 75.7 -2 0 -4.5 TGTGGGATGCTTGCTGGAGA

1132 SEQ ID NO: 4 -24.1 -26.1 75.2 -2 0 -4.5 GATGTGGGATGCTTGCTGGA

1134 SEQ ID NO: 5 -24.1 -26.1 74.9 -2 0 -4.5 TCTTCTTCCCCCTCCCCACT

1918 SEQ ID NO: 6 -23.7 -34.3 89.1 -10.6 0 0

GGGATGCTTGCTGGAGAGCT 1129 SEQ ID NO: 7 -23.6 -27.6 78.9 -2 -2 -6.9

ATGTGGGATGCTTGCTGGAG

1133 SEQ ID NO: 8 -23.5 -25.5 73.8 -2 0 -4.5 AGATGTGGGATGCTTGCTGG

1135 SEQ ID NO: 9 -23.5 -25.5 73.8 -2 0 -4.5 TGGGATGCTTGCTGGAGAGC

1130 SEQ ID NO: 10 -23.4 -26.7 76.7 -2 -1.2 -6.8

TCAGATGTGGGATGCTTGCT 1137 SEQ ID NO: 11 -23.4 -25.4 74.2 -2 0 -4.5

CAGATGTGGGATGCTTGCTG

1136 SEQ ID NO: 12 -23 -25 72.3 -2 0 -4.5 GGATGCTTGCTGGAGAGCTC

1128 SEQ ID NO: 13 -22.8 -26.8 78 -2 -2 -8

GATGCTTGCTGGAGAGCTCG 1127 SEQ ID NO: 14 -22.4 -26.4 75 -2 -2 -9.3

GGAGGCAAGGCAGCATGGTT

919 SEQ ID NO: 15 -22.3 -27.5 77.7 -4.2 -0.9 -5.7 GGCGGCATTGACTTGTTCCT

1664 SEQ ID NO: 16 -22.3 -28 77.7 -5.7 0 -6.5 CGTTCTGTCCGTTTTTCTTC

2170 SEQ ID NO: 17 -22.3 -25.2 73.9 -2.9 0 -2.6

TTTGGCAGTTCTGGTTTTCT 612 SEQ ID NO: 18 -21.8 -24.5 74.6 -2.7 0 -4.7

AGGAGGCAAGGCAGCATGGT

920 SEQ ID NO: 19 -21.7 -27.4 77.7 -5.2 -0.2 -5.4 CTCCGGCTTGTGATGCTATT

1488 SEQ ID NO: 20 -21.3 -26.4 74.2 -5.1 0.3 -6.3

AACCGTTCTGTCCGTTTTTC

2173 SEQ ID NO: 21 -21.3 -25.3 71.7 -4 0 -2.8 GTCTAAATGAGATTCCCGTT

3430 SEQ ID NO: 22 -21.3 -22.6 65.3 -0.4 -0.3 -4.1

GGGCGGCATTGACTTGTTCC

1665 SEQ ID NO: 23 -21.2 -28.3 78.3 -7.1 0 -6.5 CTTCTTCCCCCTCCCCACTC

1917 SEQ ID NO: 24 -21.2 -34.3 89.1 -13.1 0 0

AGTCTAAATGAGATTCCCG ' 3431 SEQ ID NO: 25 -21.2 -22.5 65.2 -0.4 -0.3 -4.1

GAGATTCCCGTTTTTGATTT 3422 SEQ ID NO: 26 -20.8 -22.9 66.7 -2.1 0 -2.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TCTAAATGAGATTCCCGTTT 3429 SEQ ID NO: 27 -20.8 -21.5 62.6 -0.4 0 -2.9

CTGTGCATGACTCATGAGGT 1520 SEQ ID NO: 28 -20.6 -24.4 71.9 -2.4 -0.9 -10.4

TTGGCAGTTCTGGTTTTCTA 611 SEQ ID NO: 29 -20.5 -24.1 73.6 -3.6 0 -5.4

CTAAATGAGATTCCCGTTTT

3428 SEQ ID NO: 30 -20.5 -21.2 61.6 -0.4 0 -2.6

CCTTCCTCCACGCATTCGGT

719 SEQ ID NO: 31 -20.4 -30.6 80. ≤ -9.3 -0.8 -3.8 AGATTCCCGTTTTTGATTTT

3421 SEQ ID NO: 32 -20.3 -22.4 65.7 -2.1 0 -2.6

ACCATTTCCATCCCAACTCT 2967 SEQ ID NO: 33 -20.2 -27 73.8 -6.8 0 -1

CCATTTCCATCCCAACTCTT 2966 SEQ ID NO: 34 -20.1 -26.9 73.6 -6.8 0 -1

GGGCTTTTTTCTGTTGCTTC 777 SEQ ID NO: 35 -20 -25.4 76.7 -4.9 -0.2 -3.7

GAGGCAAGGCAGCATGGTTC 918 SEQ ID NO: 36 -20 -26.7 76.9 -5.7 -0.9 -5.7

GGCAGCATGACAAGGCGACC 352 SEQ ID NO: 37 -19.9 -27.6 74.4 -6.8 -0.8 -5.3

TACTGATGGCCCGGATTTCG

1755 SEQ ID NO: 38 -19.9 -26.4 71 -6.5 0 -7.4

CGTGGCCTTGGGAAGGACAC

146 SEQ ID NO: 39 -19.8 -27.2 74 -5.9 -1.4 -8 GTCATGCTAATGGGGGATGT

967 SEQ ID NO: 40 -19.8 -24.6 71.5 -4 -0.6 -4.4

TCCGGCTTGTGATGCTATTA 1487 SEQ ID NO: 41 -19.8 -25.2 71.7 -4.7 -0.5 -6.3

TGAGATTCCCGTTTTTGATT 3423 SEQ ID NO: 42 -19.8 -22.8 66.2 -3 0 -2.6

TCGTGGCCTTGGGAAGGACA

147 SEQ ID NO: 43 -19.7 -27.4 75 -5.9 -1.8 -7.2 TCGGGTGAGCTGGTATAGGG

^' 1069 SEQ ID NO: 44 -19.7 -26.3 75.7 -6.6 0 -5 TCCTTCCTCCACGCATTCGG

720 SEQ ID NO: 45 -19.6 -29.8 78.9 -9.3 -0.8 -3.6 ACTGATGGCCCGGATTTCGG

1754 SEQ ID NO: 46 -19.6 -27.9 73.9 -6.5 -1.8 -7.4

GCAGCATGACAAGGCGACCG 351 SEQ ID NO: 47 -19.5 -27.2 71.9 -6.8 -0.8 -6.5

GGCTTTTTTCTGTTGCTTCA 776 SEQ ID NO: 48 -19.5 -24.9 75 -4.9 -0.2 -3.7

ATTGTCATGCTAATGGGGGA 970 SEQ ID NO: 49 -19.5 -23.5 68.6 -4 0 -4.4

GCATGACTCATGAGGTTGTT

1516 SEQ ID NO: 50 -19.5 -23.7 70.8 -2.4 -1.6 -10.4 GAACCGTTCTGTCCGTTTTT

2174 SEQ ID NO: 51 -19.5 -25.5 71.4 -6 0 -6.6

GTGGCCTTGGGAAGGACACA

145 SEQ ID NO: 52 -19.4 -27.1 75.2 -5.9 -1.8 -10

TGCATGACTCATGAGGTTGT

1517 SEQ ID NO: 53 -19.4 -23.6 70.2 -2.4 -1.6 -10.4 GTGCATGACTCATGAGGTTG

1518 SEQ ID NO: 54 -19.4 -23.6 70.2 -2.4 -1.6 -10.4 TGTGCATGACTCATGAGGTT

1519 SEQ ID NO: 55 -19.4 -23.6 70.2 -2.4 -1.6 -10.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GGGCAGCATGACAAGGCGAC

353 SEQ ID NO : 56 - 19 .3 -26 . 8 73 .4 -6 . 8 - 0 .5 - 5 .3 TGGCAGTTCTGGTTTTCTAT

610 SEQ ID NO : 57 - 19 . 3 -24 73 . 1 -4 . 7 0 -5 .4

GGCCCGGATTTCGGGTAGTC 1748 SEQ ID NO: 58 -19.3 -29.9 81 -6.5 -4.1 -10.5

AAGTCTAAATGAGATTCCCG 3432 SEQ ID NO: 59 -19.3 -20.6 60.2 -0.4 -0.3 -4:1

AGTTACAAGCAAGTCTTTCC 59 SEQ ID NO: 60 -19.2 -22.1 66.8 -2.9 0 -4.1

AACTCCTGTGCATGACTCAT

1525 SEQ ID NO: 61 -19.2 -24.2 69.9 -5 ^' 0 -5.4 TTCGTGGCCTTGGGAAGGAC

148 SEQ ID NO: 62 -19.1 -26.8 74.4 -5.9 -1.8 -6.5 CAGCATGACAAGGCGACCGC

350 SEQ ID NO: 63 -19.1 -27.2 71.9 -7.2 -0.8 -7.9

ACATCACCTCATCCTTTCCT 2906 SEQ ID NO: 64 -19.1 -27 76.2 -7.9 0 -0.5

TTCCCGTTTTTGATTTTAGT 3418 SEQ ID NO: 65 -19.1 -22.7 67 -3.6 0 -2.6 GTTACAAGCAAGTCTTTCCC 58 SEQ ID NO: 66 -19 -24.1 70.3 -5.1 0 -4.1 TTTCGTGGCCTTGGGAAGGA

149 SEQ ID NO: 67 -19 -26.7 74.1 -5.9 -1.8 -7.2 CAAATTTCGTGGCCTTGGGA

153 SEQ ID NO: 68 -19 -24.9 69 -5.9 0 -7.2 CGGGTGAGCTGGTATAGGGG

1068 SEQ ID NO: 69 -19 -27.1 76.6 -8.1 0 -5

GTATCAGATGTGGGATGCTT 1140 SEQ ID NO: 70 -19 -23.6 70.7 -4.6 0 -4.2

GTCCAGCAGGGCGGCATTGA 1673 SEQ ID NO: 71 -19 -30.2 82.3 -10.1 -1 -6.8

TTCTTCCCCCTCCCCACTCC 1916 SEQ ID NO: 72 -19 -35.4 90.4 -16.4 0 0

TGGGCAGCATGACAAGGCGA

354 SEQ ID NO: 73 -18.9 -26.6 72.7 -6.8 -0.8 -5.3 GCCCAAAGGTGCTCAGCTTT

1254 SEQ ID NO: 74 -18.9 -28.2 77.8 -7.8 -1.4 -3.5 TAACTCCTGTGCATGACTCA

1526 SEQ ID NO: 75 -18.9 -23.9 69.4 -5 0 -5.4 GCCCGGATTTCGGGTAGTCG

1747 SEQ ID NO: 76 -18.9 -29.5 78.1 -6.5 -4.1 -10.5

GTTCTGTCCGTTTTTCTTCT 2169 SEQ ID NO: 77 -18.9 -25.3 76.2 -6.4 0 -2.6

TCAAATTTCGTGGCCTTGGG

154 SEQ ID NO: 78 -18.8 -24.7 69.2 -5.9 0 -7.2 CTTCCTCCACGCATTCGGTC

718 SEQ ID NO: 79 -18.8 -29 78.9 -9.3 -0.8 -3.8

TTCTGTTGCTTCAGGGCCCT 769 SEQ ID NO: 80 -18.8 -29.7 84 -9.2 -0.7 -11.5

GGTATAGGGGTCTGGGTACT 1058 SEQ ID NO: 81 -18.8 -26.3 78.4 -7 -0.2 -5.8

AGCCCAAAGGTGCTCAGCTT

1255 SEQ ID NO: 82 -18.8 . -28.1 77.8 -7.8 -1.4 -8.1 GCTCCGGCTTGTGATGCTAT

1489 SEQ ID NO: 83 -18.8 -28.1 78.1 -8.6 -0.5 -6.3 ATTTCGTGGCCTTGGGAAGG

150 SEQ ID NO: 84 -18.7 -26.1 72.8 -5.9 -1.4 -7.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTCCTTCCTCCACGCATTCG

721 SEQ ID NO: 85 -18.7 -28.7 76.8 -9.3 -0.4 -3.6 GGCCCAAACTTATTCCTTCC

733 SEQ ID NO: 86 -18.7 -27.1 73.6 -8.4 0 -5.6 TTGTCATGCTAATGGGGGAT

969 SEQ ID NO: 87 -18.7 -23.5 68.6 -4 -0.6 -4.4 CTCCTGTGCATGACTCATGA

1523 SEQ ID NO: 88 -18.7 -25.3 72.9 -5 -1.6 -8.6 CCAGCAGGGCGGCATTGACT

1671 SEQ ID NO: 89 -18.7 -29.7 79.5' -10.1 -0.8 -6.8 CTCTTGTAAATCCCCAGTAT

260 SEQ ID NO: 90 -18.6 -23.8 68.2 -5.2 0 -1.8 GACTCTTGTAAATCCCCAGT

262 SEQ ID NO: 91 -18.6 -24.9 70.7 -6.3 0 -2.7 ATTCCTTCCTCCACGCATTC

722 SEQ ID NO: 92 -18.6 -27.9 77.1 -9.3 0 -3.6 TGGCCCAAACTTATTCCTTC

734 SEQ ID NO: 93 -18.6 -25.1 70.1 -6.5 0 -6.6 TGTCATGCTAATGGGGGATG

968 SEQ ID NO: 94 -18.6 -23.4 68.1 -4 -0.6 -4.4 TCCATGTACCACTTGTCGGT

1418 SEQ ID NO: 95 -18.6 -26.9 75.7 -7.8 -0.1 -4.7 ACTCCTGTGCATGACTCATG

1524 SEQ ID NO: 96 -18.6 -24.9 72.2 -5 -1.2 -8.1 TGATGGCCCGGATTTCGGGT

1752 SEQ ID NO: 97 -18.6 -29.2 77.1 -6.5 -4.1 -11.8 CTGATGGCCCGGATTTCGGG

1753 SEQ ID NO: 98 -18.6 -28.9 75.7 -6.5 -3.8 -9.8 GAGGAATCCTGTAAGCTCAA

2271 SEQ ID NO: 99 -18.6 -22.3 65.3 -3 -0.5 -7.8 ATGAGATTCCCGTTTTTGAT

3424 SEQ ID NO: 100 -18.6 -22.7 65.8 -4.1 0 -2.6 ATGCTTGCTGGAGAGCTCGT

1126 SEQ ID NO: 101 -18.5 -27 77.2 -6.5 -2 -9.3 TTGGGCAGCATGACAAGGCG

355 SEQ ID NO: 102 -18.4 -26.1 71.8 -6.8 -0.8 -€.5 ATTTGGCAGTTCTGGTTTTC

613 SEQ ID NO: 103 -18.4 -23.6 72.4 -5.2 0 -5.4 TGTCATAGTCTGTAGGAGGC

933 SEQ ID NO: 104 -18.4 -24.2 74.6 -5.8 0 -2.8 TGGTATAGGGGTCTGGGTAC

1059 SEQ ID NO: 105 -18.4 -25.4 76 -7 0 -4 GCTTGCTGGAGAGCTCGTCT

1124 SEQ ID NO: 106 -18.4 -28.3 81.4 -7.9 -2 -9.3 CCTGTGCATGACTCATGAGG

1521 SEQ ID NO: 107 -18.4 -25.2 72.2 -5.1 -1.6 -10.4 AGGGCGGCATTGACTTGTTC

1666 SEQ ID NO: 108 -18.4 -26.3 75.1 -7.9 0 -6.5 CCCGGATTTCGGGTAGTCGA

1746 SEQ ID NO: 109 -18.4 -28.3 75.4 -6.5 -3.4 -11.6 GATGGCCCGGATTTCGGGTA

1751 SEQ ID NO: 110 -18.4 -28.9 76.7 -6.5 -4 -11.8 TCTTCCTGTTCTTCTTCCCC

1927 SEQ ID NO: 111 -18.4 -29.2 83.6 -10.8 0 0 ATGGAGGAATCCTGTAAGCT

2274 SEQ ID NO: 112 -18.4 -23.1 67.3 -1.9 -2.8 -9.8 AATTTCGTGGCCTTGGGAAG

151 SEQ ID NO: 113 -18.3 -24.2 68.1 -5.9 0 -7.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GCTTTTTTCTGTTGCTTCAG 775 SEQ ID NO: 114 -18.3 -23.7 72.5 -4.9 -0.1 -5.4

TAGGAGGCAAGGCAGCATGG 921 SEQ ID NO: 115 -18.3 -25.9 73.6 -6.6 -0.9 -5.7

TGCTTGCTGGAGAGCTCGTC 1125 SEQ ID NO: 116 -18.3 -27.4 79.1 -7.6 -1.4 -9.3

CCGGCTTGTGATGCTATTAT 1486 SEQ ID NO: 117 -18.3 -24.8 70.1 -5.8 -0.5 -5.'2

GCTCTTTTGGCATGCAACAT

1846 SEQ ID NO: 118 -18.3 -24.7 71 -5.2 -0.5 -10.1 TGGCCTTGGGAAGGACACAT

144 SEQ ID NO: 119 -18.2 -25.9 71.9 -5.9 -1.8 -7.2

TCCAGCAGGGCGGCATTGAC 1672 SEQ ID NO: 120 -18.2 -29.2 79.4 -10.1 -0.8 -6.8

TGCTCTTTTGGCATGCAACA

1847 SEQ ID NO: 121 -18.2 -24.7 70.9 -5.2 -1 -10.1 TTCTTCCTGTTCTTCTTCCC

1928 SEQ ID NO: 122 -18.2 -27.3 80.3 -9.1 0 0

GCATTCTTGAGAATTGTTTC 2308 SEQ ID NO: 123 -18.2 -20.4 63.3 -1.6 -0.2 -7.6

TTCCATCCCAACTCTTGAGG 2962 SEQ ID NO: 124 -18.2 -25.9 72.6 -6.8 -0.7 -5.2

GTGAAATTATAGGCAGTTCT 219 SEQ ID NO: 125 -18.1 -20.2 62.2 -2.1 0 -4

TTTCTCTGTCTGCTGCGGGT 1709 SEQ ID NO: 126 -18.1 -28.2 81.8 -10.1 0 -7

CATTTCCATCCCAACTCTTG 2965 SEQ ID NO: 127 -18.1 -24.9 70 -6.8 0 -2.4

TTGGCCCAAACTTATTCCTT 735 SEQ ID NO: 128 -18 -24.8 68.9^' -6.8 0 -6.6

CATTGTCATGCTAATGGGGG 971 SEQ ID NO: 129 -18 -23.6 68.4 -4.8 -0.6 -6.3

TTCCATGTACCACTTGTCGG 1419 SEQ ID NO: 130 -18 -25.8 72.7 -7.8 0 -4.3

TCCCCCTCCCCACTCCCCCA 1912 SEQ ID NO: 131 -18 -40.6 95.6 -22.6 0 0

GGAATCCTGTAAGCTCAAAT

2269 SEQ ID NO: 132 -18 -21 61.8 -3 0 -5.6 AGGAATCCTGTAAGCTCAAA

2270 SEQ ID NO: 133 -18 -21 62 -3 0 -7.1 CATCACCTCATCCTTTCCTT

2905 SEQ ID NO: 134 -18 -26.9 76 -8.9 0 -0.5

TCCATCCCAACTCTTGAGGA 2961 SEQ ID NO: 135 -18 -26.4 73.5 -6.8 -1.6 -5.9

ATTTCCATCCCAACTCTTGA 2964 SEQ ID NO: 136 -18 -24.8 70.1 -6.8 0 -2.6

AAAGTTACAAGCAAGTCTTT 61 SEQ ID NO: 137 -17.9 -18.3 57.2 0 0 -4.4

GGCAGTTCTGGTTTTCTATA 609 SEQ ID NO: 138 -17.9 -23.7 72.7 -5.8 0 -5.4

CAATTTGGCAGTTCTGGTTT 615 SEQ ID NO: 139 -17.9 -23.1 69 -5.2 0 -5.4

TATTCCTTCCTCCACGCATT 723 SEQ ID NO: 140 -17.9 -27.2 74.8 -9.3 0 -3.6

AGGGCTTTTTTCTGTTGCTT 778 SEQ ID NO: 141 -17.9 -25 75.1 -6.6 -0.2 -3.7

AAGCCCAAAGGTGCTCAGCT 1256 SEQ ID NO: 142 -17.9 -27.3 75 -7.8 -1.5 -7.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GTTCTTCTTCCCCCTCCCCA 1920 SEQ ID NO: 143 -17.9 -34.5 90.7 -16.6 0 0

TTAGTTCCTAAATTTCTTCA 2220 SEQ ID NO: 144 -17.9 -19.4 60.5 -1.4 0 -4.9

TACATCACCTCATCCTTTCC 2907 SEQ ID NO: 145 -17.9 -25.8 73.7 -7.9 0 -0.5

GTCAATACATCACCTCATCC 2912 SEQ ID NO: 146 -17.9 -23.9 69.4 -6 0 -2

GTTGCTTCAGGGCCCTGTCT 765 SEQ ID NO: 147 -17.8 -30.8 87.4 -9.2 -0.7 -15.8

GTATAGGGGTCTGGGTACTC 1057 SEQ ID NO: 148 -17.8 -25.5 77.5 -7 -0.5 -5.8

GCAGGGCGGCATTGACTTGT 1668 SEQ ID NO: 149 -17.8 -28.3 78.4 -10.5 0 -5.9

AGTTCCTAAATTTCTTCATA

2218 SEQ ID NO: 150 -17.8 -19.3 60.2 -1.4 0 -4.9 TAGTTCCTAAATTTCTTCAT

2219 SEQ ID NO: 151 -17.8 -19.3 60.2 -1.4 0 -4.9 TGCATTCTTGAGAATTGTTT

2309 SEQ ID NO: 152 -17.8 -20 61.7 -1.6 -0.2 -7.6

AAAGTCTAAATGAGATTCCC 3433 SEQ ID NO: 153 -17.8 -19.1 57.8 -0.4 -0.3 -4.1

ACTCTTGTAAATCCCCAGTA 261 SEQ ID NO: 154 -17.7 -24 68.8 -6.3 0 -2.3

CGGTCCGGAAGCCCAGCACC 307 SEQ ID NO: 155 -17.7 -32.7 81.9 -13.7 -0.7 -10.4

CCATGTACCACTTGTCGGTA 1417 SEQ ID NO: 156 -17.7 -26.2 73.4 -7.8 -0.4 -5.8

GCGGCATTGACTTGTTCCTG 1663 SEQ ID NO: 157 -17.7 -26.8 74.9 -9.1 0 -5.9

TTCTCTGTCTGCTGCGGGTA 1708 SEQ ID NO: 158 -17.7 -27.8 80.7 -10.1 0 -7

GCATACTGATGGCCCGGATT

1758 SEQ ID NO: 159 -17.7 -27.6 74.2 -9.1 -0.6 -7.5 TCCATTAGTACAGATTCGGT

2394 SEQ ID NO: 160 -17.7 -23 68 -5.3 0 -5.3

GTCCATTAGTACAGATTCGG 2395 SEQ ID NO: 161 -17.7 -23 68 -5.3 0 -5.3

AAATTTCGTGGCCTTGGGAA 152 SEQ ID NO: 162 -17.6 -23.5 65.8 -5.9 0 -7.2

GTCGGTCCGGAAGCCCAGCA 309 SEQ ID NO: 163 -17.6 -32.1 83.2 -13.4 -0.7 -9.8

CCCAAAGGTGCTCAGCTTTT 1253 SEQ ID NO: 164 -17.6 -26.5 74 -7.8 -1 -3.8

TGGATCCTTCCTTTCCATGT 1431 SEQ ID NO: 165 -17.6 -27 76.6 -7.8 -1.6 -8.5

TCTCTGTCTGCTGCGGGTAG 1707 SEQ ID NO: 166 -17.6 -27.7 80.7 -10.1 10 -7

TGCATACTGATGGCCCGGAT

1759 SEQ ID NO: 167 -17.6 -27.5 73.7 -9.1 -0.6 -7.5 TCAATACATCACCTCATCCT

2911 SEQ ID NO: 168 -17.6 -23.6 68.1 -6 0 -1.2

TAAAGTTACAAGCAAGTCTT 62 SEQ ID NO: 169 -17.5 -17.9 56.3 0 0 -4.1

TTTGGGCAGCATGACAAGGC 356 SEQ ID NO: 170 -17.5 -25.4 72.2 -6.8 -1 -8.2

CTGTCATAGTCTGTAGGAGG 934 SEQ ID NO: 171 -17.5 -23.3 71.9 -5.8 0 -2.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TCTTCCCCCTCCCCACTCCC 1915 SEQ ID NO: 172 -17.5 -37.3 93.1 -19.8 0 0

TACAATGTCTTTTATATGGA

2109 SEQ ID NO: 173 -17.5 -17.9 56.8 0 0 -4.6

ATAAAGTTACAAGCAAGTCT

63 SEQ ID NO: 174 -17.4 -17.8 56 0 0 -4.1 AGACTCTTGTAAATCCCCAG

263 SEQ ID NO: 175 -17.4 -23.7 67.7 -6.3 0 -2 '.4

AGCATGACAAGGCGACCGCG 349 SEQ ID NO: 176 -17.4 -27.3 70.9 -8.9 -0.8 -9.1

AATCCCTTGCAGCTTTCACA 550 SEQ ID NO: 177 -17.4 -26.1 73.5 -8.7 0 -5.2

CTGTTGCTTCAGGGCCCTGT 767 SEQ ID NO: 178 -17.4 -30.4 85.1 -9.2 -0.3 -15.8

AGGCAAGGCAGCATGGTTCA 917 SEQ ID NO: 179 -17.4 -26.8 76.6 -8.4 -0.9 -5.7

CTAACTCCTGTGCATGACTC 1527 SEQ ID NO: 180 -17.4 -24.1 70.2 -6.7 0 -5.4

TTTCCATCCCAACTCTTGAG 2963 SEQ ID NO: 181 -17.4 -24.8 70.4 -6.8 . -0.3 -4.7

GGTCCGGAAGCCCAGCACCA 306 SEQ ID NO: 182 -17.3 -32.6 83.3 -13.7 -0.7 -11

AATTTGGCAGTTCTGGTTTT 614 SEQ ID NO: 183 -17.3 -22.5 68.1 -5.2 0 -5.4

GGGGGATGTTACAAAGGGAC 956 SEQ ID NO: 184 -17.3 -23.1 66.8 -5.8 0 -3.1

TATAGGGGTCTGGGTACTCA 1056 SEQ ID NO: 185 -17.3 -25 74.8 -7 -0.5 -6.3

CCGGATTTCGGGTAGTCGAA 1745 SEQ ID NO: 186 -17.3 -25.6 69.8 -6.5 -1.8 -9.2

AGGTCCATTAGTACAGATTC 2397 SEQ ID NO: 187 -17.3 -22.2 68.1 -4.9 0 -5.3

CAATACATCACCTCATCCTT

2910 SEQ ID NO: 188- -17.3 -23.3 66.9 -6 0 -1.2

CATAAAGTTACAAGCAAGTC

64 SEQ ID NO: 189 -17.2 -17.6 55.4 0 0 -4.1 TCATAAAGTTACAAGCAAGT

65 SEQ ID NO: 190 -17.2 -17.6 55.4 0 0 -4.1 GTCATAGTCTGTAGGAGGCA

932 SEQ ID NO: 191 -17.2 -24.9 76 -6.9 -0.6 -4

TATCAGATGTGGGATGCTTG 1139 SEQ ID NO: 192 -17.2 -22.4 67.1 -5.2 0 -3.6

GTTGAGGGTGGCTCCGGCTT 1499 SEQ ID NO: 193 -17.2 -30.6 84.8 -12 -1.3 -6.6

CCCAACTCTTGAGGATGTTC 2956 SEQ ID NO: 194 -17.2 -24.6 70.7 -6.8 -0.3 -4.8 TTACAAGCAAGTCTTTCCCT 57 SEQ ID NO: 195 -17.1 -23.8 69 -6.7 0 -4.1

TGTCGGTCCGGAAGCCCAGC 310 SEQ ID NO: 196 -17.1 -31.4 82 -13.4 -0.7 -8.8

ATGACAAGGCGACCGCGGGC 346 SEQ ID NO: 197 -17.1 -29 74.1 -10.2 -0.7 -11.5

CAGCATGGTTCAGAGGTAGG 909 SEQ ID NO: 198 -17.1 -24.7 73.7 -7.6 0 -5

CTTCTGTCATAGTCTGTAGG 937 SEQ ID NO: 199 -17.1 -22.9 71.6 -5.8 0 -2.2

ATAGGGGTCTGGGTACTCAG 1055 SEQ ID NO: 200 -17.1 -25.3 75.8 -7 -0.9 -9.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GGGTGAGCTGGTATAGGGGT 1067 SEQ ID NO: 201 -17.1 -27.5 80.7 -10.4 0 -4.4

TGAGGGTGGCTCCGGCTTGT 1497 SEQ ID NO: 202 -17.1 -30.5 84.2 -12 -1.3 -6.6

TGTTGAGGGTGGCTCCGGCT 1500 SEQ ID NO: 203 -17.1 -30.5 84.2 -12 -1.3 -6.6

ACAATGTCTTTTATATGGAA 2108 SEQ ID NO: 204 -17.1 -17.5 55.4 0 0 -4

ATGCATTCTTGAGAATTGTT 2310 SEQ ID NO: 205 -17.1 -19.9 61.3 -2.3 -0.2 -7.6

GGCCTTCAAAGGAAGAGGGA 2352 SEQ ID NO: 206 -17.1 -24.4 68.9 -5.3 -2 -7

ATTCCCGTTTTTGATTTTAG 3419 SEQ ID NO: 207 -17.1 -21.5 63.8 -4.4 0 -2.1

TGAAATTATAGGCAGTTCTT 218 SEQ ID NO: 208 -17 -19.1 59.4 -2.1 0 -4

TTCCTCCACGCATTCGGTCG 717 SEQ ID NO: 209 -17 -28.9 76.7 -11 -0.8 -3.8

ATACTGATGGCCCGGATTTC 1756 SEQ ID NO: 210 -17 -25.6 71 -8.6 0 -6.6

TTACAATGTCTTTTATATGG 2110 SEQ ID NO: 211 -17 -17.4 55.8 0 0 -4.6

CTATGGAGCATTTGCTTTGA 2648 SEQ ID NO: 212 -17 -22.6 67.1 -4.6 -0.9 -8.5

CCATCCCAACTCTTGAGGAT 2960 SEQ ID NO: 213 -17 -26 71.9 -6.8 -2.2 -6.7

AAGTTACAAGCAAGTCTTTC 60 SEQ ID NO: 214 -16.9 -19.4 60.6 -2.5 0 -4.1

ATTGGCCCAAACTTATTCCT 736 SEQ ID NO: 215 -16.9 -24.7 68.6 -7.8 0 -6.6

TGTTGCTTCAGGGCCCTGTC 766 SEQ ID NO: 216 -16.9 -29.9 85.1 -9.2 -0.7 -15.8

TCTGTTGCTTCAGGGCCCTG 768 SEQ ID NO: 217 -16.9 -29.6 83.3 -9.2 -0.7 -15.2

TTTCCATGTACCACTTGTCG 1420 SEQ ID NO: 218 -16.9 -24.7 70.5 -7.8 0 -4.3

TCCTTCCTTTCCATGTACCA 1427 SEQ ID NO: 219 -16.9 -27.8 77.6 -10.9 0 -4.3

CCCCCTCCCCACTCCCCCAA 1911 SEQ ID NO: 220 -16.9 -39.5 91.3 -22.6 0 0

CAATGTCTTTTATATGGAAT 2107 SEQ ID NO: 221 -16.9 -17.3 54.9 0 0 -2.4

GATTAGTTCCTAAATTTCTT 2222 SEQ ID NO: 222 -16.9 -18.9 59.2 -1.4 -0.2 -4.9

TTCTTGAGAATTGTTTCAGT 2305 SEQ ID NO: 223 -16.9 -19.8 62.5 -1.6 -1.2 -5.5

TTAGTACAGATTCGGTGACC 2390 SEQ ID NO: 224 -16.9 -22.7 67.1 -5.8 10 -5.3

TATGGAGCATTTGCTTTGAA 2647 SEQ ID NO: 225 -16.9 -21 63 -3.5 -0.3 -7.9

AATGAGATTCCCGTTTTTGA 3425 SEQ ID NO: 226 -16.9 -22 63.8 -5.1 0 -2.6

GTCAAATTTCGTGGCCTTGG 155 SEQ ID NO: 227 -16.8 -24.7 69.9 -7.9 0 -7.2

TCAATTTGGCAGTTCTGGTT 616 SEQ ID NO: 228 -16.8 -23.4 70.3 -6.6 0 -5.8

TTATTCCTTCCTCCACGCAT 724 SEQ ID NO: 229 -16.8 -27.2 74.8 -10.4 0 -3.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTCTGTCATAGTCTGTAGGA 936 SEQ ID NO: 230 -16.8 -22.6 70.9 -5.8 0 -3

AGATTAGTTCCTAAATTTCT

2223 SEQ ID NO: 231 -16.8 -18.8 59 -1.4 -0.2 -4.9

AATCACCATTTCCATCCCAA

2971 SEQ ID NO: 232 -16.8 -25 68.5 -8.2 0 -1.5 AAATCACCATTTCCATCCCA

2972 SEQ ID NO: 233 -16.8 -25 68.5 -8.2 0 -2.5 TCCCGTTTTTGATTTTAGTG

3417 SEQ ID NO: 234 -16.8 -22.6 66.6 -5.8 0 -2.6

AAGACTCTTGTAAATCCCCA 264 SEQ ID NO: 235 -16.7 -23 65.4 -6.3 0 -3.9

TCTAGCTTCATTCCAACACT 685 SEQ ID NO: 236 -16.7 -23.4 68.9 -6.7 0 -4.6

GCCCAAACTTATTCCTTCCT 732 SEQ ID NO: 237 -16.7 -26.8 73 -10.1 0 -2

TCTGTCATAGTCTGTAGGAG 935 SEQ ID NO: 238 -16.7 -22.5 70.8 -5.8 0 -3

TAAGCCCAAAGGTGCTCAGC 1257 SEQ ID NO: 239 -16.7 -26.1 72.5 -7.8 . -1.5 -8.2

CCTTCCTTTCCATGTACCAC 1426 SEQ ID NO: 240 -16,7 -27.6 76.4 -10.9 0 -4.3

CTCTTTTGGCATGCAACATT 1845 SEQ ID NO: 241 -16.7 -23 67.1 -5.2 -0.2 -10.1

ATTAGTTCCTAAATTTCTTC 2221 SEQ ID NO: 242 -16.7 -18.7 59.2 -1.4 -0.2 -4.9

ATCACCTCATCCTTTCCTTT 2904 SEQ ID NO: 243 -16.7 -26.3 75.3 -9.6 0 -0.5

GGCCTTGGGAAGGACACATC 143 SEQ ID NO: 244 -16.6 -26.3 73.7 -7.9 -1.8 -6.4

TAGGGGTCTGGGTACTCAGA 1054 SEQ ID NO: 245 -16.6 -25.9 77.3 -7 -2.1 -12

GTTCCAGTATCAGATGTGGG 1146 SEQ ID NO: 246- -16.6 -24.6 73.5 -7.4 -0.3 -5.9

CTTATGCTCTTTTGGCATGC 1851 SEQ ID NO: 247 -16.6 -24.5 72.1 -5.8 ^• -2.1 -8.9

AGAACCGTTCTGTCCGTTTT 2175 SEQ ID NO: 248 -16.6 -25.4 71.3 -8.1 -0.5 -8.1

TCGGTCCGGAAGCCCAGCAC 308 SEQ ID NO: 249 -16.5 -31.1 80.4 -13.5 -0.7 -9.8

AGTATCAGATGTGGGATGCT 1141 SEQ ID NO: 250 -16.5 -23.5 70.6 -6.1 -0.7 -4.8

GGATCCTTCCTTTCCATGTA 1430 SEQ ID NO: 251 -16.5 -26.7 76.2 -9.2 -0.9 -7.7

TTGTTGAGGGTGGCTCCGGC 1501 SEQ ID NO: 252 -16.5 -29.7 82.6 -12 -1.1 -6.6

TTTCAAGGTTTTTGACATCT 1620 SEQ ID NO: 253 -16.5 -20.2 62.6 -2.3 -1.3 -4.8

CATTACAATGTCTTTTATAT 2112 SEQ ID NO: 254 -16.5 -16.9 54.6 1 0 -4.6

GCAGCTTTCACAGGTGAGGA 542 SEQ ID NO: 255 -16.4 -26.2 76.8 -7.9 -1.9 -7.1

ATCAGATGTGGGATGCTTGC 1138 SEQ ID NO: 256 -16.4 -24.5 72.1 -8.1 0 -3.6

GACTCATGAGGTTGTTGAGG 1512 SEQ ID NO: 257 -16.4 -23 69.5 -5 -1.5 -10.4

ATTTCTCTGTCTGCTGCGGG 1710 SEQ ID NO: 258 -16.4 -27 78 -10.6 0 -7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTATGCTCTTTTGGCATGCA 1850 SEQ ID NO: 259 -16.4 -24.3 71.3 -5.8 -2.1 -10.1

GGAGGAATCCTGTAAGCTCA 2272 SEQ ID NO: 260 -16.4 -24.2 70.1 -5.7 -2.1 -9.2

CATTCTTGAGAATTGTTTCA 2307 SEQ ID NO: 261 -16.4 -19.3 60.3 -1.6 -1.2 -7.6

CCTTGAGTCAATACATCACC 2918 SEQ ID NO: 262 -16.4 -23.1 67 -6 -0.4 -7.6

TCCCAACTCTTGAGGATGTT 2957 SEQ ID NO: 263 -16.4 -24.6 70.7 -6.8 -1.3 -5.7

GAAATTATAGGCAGTTCTTT 217 SEQ ID NO: 264 -16.3 -19.2 59.8 -2.9 0 -4

TTATTTTGGACTGTTCGCTT

574 SEQ ID NO: 265 -16.3 -22.3 66.5 -5.5 -0.1 -4 GGGGATGTTACAAAGGGACT

955 SEQ ID NO: 266 -16.3 -22.8 66.2 -5.8 -0.4 -3.7

TGCTGGAGAGCTCGTCTGGT 1121 SEQ ID NO: 267 -16.3 -27.9 80.5 -9.6 -2 ^• -9.3

TTTCTTCCTGTTCTTCTTCC 1929 SEQ ID NO: 268 -16.3 .-25.4 76.8 -9.1 0 0

AGACAAAACAACCCTCAGAA 2542 SEQ ID NO: 269 -16.3 -19.7 57.3 -3.4 0 -2.5

AGCTTTCACAGGTGAGGAGC 540 SEQ ID NO: 270 -16.2 -25.5 75.9 -8.4 -0.7 -8.7

CGCTTAAAAAATCCCTTGCA 559 SEQ ID NO: 271 -16.2 -21.7 60.4 -5.5 0 -4.8

ATTATTTTGGACTGTTCGCT

575 SEQ ID NO: 272 -16.2 -22.2 66.2 -5.5 -0.1 -4 AGTTCTGGTTTTCTATACAT

606 SEQ ID NO: 273 -16.2 -20.9 65.7 -4.7 0 -2.6

CCAAAGGTGCTCAGCTTTTC 1252 SEQ ID NO: 274 -16.2 -24.9 72 -8 -0.5 -3.8

GTTTTGAAAGCAGAGCTCCT 1882 SEQ ID NO: 275 -16.2 -23.8 69.6 -6.7 -0.8 -8.4

TCTTGAGAATTGTTTCAGTT 2304 SEQ ID NO: 276 -16.2 -19.8 62.5 -2.3 -1.2 -3.9

GGTCCATTAGTACAGATTCG 2396 SEQ ID NO: 277 -16.2 -23 68 -6.8 0 -5.3

TTCATAAAGTTACAAGCAAG 66 SEQ ID NO: 278 -16.1 -16.5 52.8 0 0 -4.1

CTTGTCAAATTTCGTGGCCT 158 SEQ ID NO: 279 -16.1 -24.4 69.3 -8.3 0 -7.2

GTAGGAGGCAAGGCAGCATG 922 SEQ ID NO: 280 -16.1 -25.9 74.4 -8.8 -0.9 -5.3

ACTTCTGTCATAGTCTGTAG 938 SEQ ID NO: 281 -16.1 -21.9 69.3 -5.8 0 -3.2

ATGGATCCTTCCTTTCCATG 1432 SEQ ID NO: 282 -16.1 -25.8 73.1 -7.9 -1.8 -8.5

TTCAAGGTTTTTGACATCTA 1619 SEQ ID NO: 283 -16.1 -19.8 61.6 -2.3 -1.3 -4.8

TCTGTCTGCTGCGGGTAGTT 1705 SEQ ID NO: 284 -16.1 -27.7 80.9 -11.6 0 -6.5

CCATTACAATGTCTTTTATA 2113 SEQ ID NO: 285 -16.1 -18.9 58.5 -2.8 0 -5.1

CACCATTTCCATCCCAACTC 2968 SEQ ID NO: 286 -16.1 -26.8 73 -10.7 0 -1

TGACAAGGCGACCGCGGGCG 345 SEQ ID NO: 287 -16 -29.8 74 -11.9 -0.8 -12 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CATGACAAGGCGACCGCGGG 347 SEQ ID NO: 288 -16 -27.9 71.4 -10.2 -0.7 -11.5

AAATCCCTTGCAGCTTTCAC 551 SEQ ID NO: 289 -16 -24.7 70 -8.7 0 -5.2

AGTCTGTAGGAGGCAAGGCA 927 SEQ ID NO: 290 -16 -25.9 76.2 -9 -0.7 -4.6

AGTTCCAGTATCAGATGTGG 1147 SEQ ID NO: 291 -16 -23.4 71 -7.4 0 -5 '.3

GAGAGTTTGATCTGCCATTT

1283 SEQ ID NO: 292 -16 -23.2 69.2 -7.2 0 -4.9 TTGAGGGTGGCTCCGGCTTG

1498 SEQ ID NO: 293 -16 -29.4 81 -12 -1.3 -6.6

TCCTGTGCATGACTCATGAG 1522 SEQ ID NO: 294 -16 -24.4 71.2 -6.8 -1.6 -9.9

CTGCATACTGATGGCCCGGA 1760 SEQ ID NO: 295 -16 -28.4 75.5 -11.6 -0.6 -7.5

GTATTCTTCAGCCTGCATAC 1772 SEQ ID NO: 296 -16 -24.6 73 -8.6 0 -4.9

TGTTCTTCTTCCCCCTCCCC 1921 SEQ ID NO: 297 -16 -33.8 89.5 -17.8 0 0

TGGAGGAATCCTGTAAGCTC 2273 SEQ ID NO: 298 -16 -23.5 68.8 -4.7 -2.8 -10

GTGTCGGTCCGGAAGCCCAG 311 SEQ ID NO: 299 -15.9 -30.8 81.2 -14 -0.7 -8.3

TCGCTTAAAAAATCCCTTGC 560 SEQ ID NO: 300 -15.9 -21.4 60.5 -5.5 0 -3.2

TATTTTGGACTGTTCGCTTA 573 SEQ ID NO: 301 -15.9 -21.9 65.6 -5.5 -0.1 -4

TTCTAGCTTCATTCCAACAC 686 SEQ ID NO: 302 -15.9 -22.6 67.3 -6.7 0 -4.6

TTGCTTCAGGGCCCTGTCTC 764 SEQ ID NO: 303 -15.9 -30 85.5 -10.3 -0.7 -15.8

CTCGGGTGAGCTGGTATAGG 1070 SEQ ID NO: 304 -15.9 -26 75 -9.4 -0.4 -5

AGAGAGTTTGATCTGCCATT

1284 SEQ ID NO: 305 -15.9 -23.1 69.1 -7.2 0 -4.9 TGCAGCTTTCACAGGTGAGG

543 SEQ ID NO: 306 -15.8 -25.6 75.1 -7.9 -1.9 -7.1

GGCAAGGCAGCATGGTTCAG 916 SEQ ID NO: 307 -15.8 -26.8 76.6 -10 -0.9 -5.7

CCAGTATCAGATGTGGGATG 1143 SEQ ID NO: 308 -15.8 -23.5 69.1 -7.7 0 -4.9

GTGGCTCCGGCTTGTGATGC 1492 SEQ ID NO: 309 -15.8 -29.9 82.8 -12.7 -1.3 -6.3

GTTGTTGAGGGTGGCTCCGG

1502 SEQ ID NO: 310 -15.8 -29.1 81.8 -12 -1.2 -6.4 GGTTGTTGAGGGTGGCTCCG

1503 SEQ ID NO: 311 -15.8 -29.1 81.8 -12 -1.2 -5 CAGGGCGGCATTGACTTGTT

1667 SEQ ID NO: 312 -15.8 -26.6 74.5 -10.8 0 -6.5

CTTTTGGCATGCAACATTTC

1843 SEQ ID NO: 313 -1.5.8 -22.2 65.5 -5.2 -0.5 -10.1 TCTTTTGGCATGCAACATTT

1844 SEQ ID NO: 314 -15.8 -22.2 65.5 -5.2 -0.5 -10.1 AATGTCTTTTATATGGAATC-

2106 SEQ ID NO: 315 -15.8 -17 54.9 -1.1 0 -2.4

ATTACAATGTCTTTTATATG 2111 SEQ ID NO: 316 -15.8 -16.2 53.2 0 0 -4.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GAGACAAAACAACCCTCAGA 2543 SEQ ID NO: 317 -15.8 -21 60.2 -5.2 0 -3.6

ATACATCACCTCATCCTTTC 2908 SEQ ID NO: 318 -15.8 -23.8 70 -8 0 -0.9

ATTAAGGAAATTACCGCTTT 3339 SEQ ID NO: 319 -15.8 -19.2 57.2 -3.4 0.3 -3.3

GATTCCCGTTTTTGATTTTA 3420 SEQ ID NO: 320 -15.8 -22.1 64.9 -6.3 0 -2.6

GCCTTGGGAAGGACACATCA 142 SEQ ID NO: 321 -15.7 -25.8 72.2 -8.3 -1.8 -6

GGGGTCTGGGTACTCAGACT 1052 SEQ ID NO: 322 -15.7 -27.3 80.4 -7 -4.6 -16.3

CTGGTATAGGGGTCTGGGTA 1060 SEQ ID NO: 323 -15.7 -26.1 77.5 -10.4 0 -2.2

CATGACTCATGAGGTTGTTG 1515 SEQ ID NO: 324 -15.7 -21.9 66.2 -5.1 -0.9 -9.5

AGCAGGGCGGCATTGACTTG 1669 SEQ ID NO: 325 -15.7 -27.1 75.3 -10.5 -0.8 -6.7

TATTCTTCAGCCTGCATACT 1771 SEQ ID NO: 326 -15.7 -24.3 71.5 -8.6 0 -4.9

TGTTTTGAAAGCAGAGCTCC 1883 SEQ ID NO: 327 -15.7 -22.9 67.5 -6.3 -0.8 -8.4

TCCTGTAAGCTCAAATCCCC 2265 SEQ ID NO: 328 -15.7 -26.3 72.2 -10.6 0 -5

ATTCTTGAGAATTGTTTCAG 2306 SEQ ID NO: 329 -15.7 -18.6 59.2 -1.6 -1.2 -7.3

TTTGTTTCCAACTACTTAGA 2856 SEQ ID NO: 330 -15.7 -20.3 62.2 -3.9 -0.5 -3.2

GTCCGGAAGCCCAGCACCAA 305 SEQ ID NO: 331 -15.6 -30.7 78.6 -13.7 -1.2 -9.8

CTTGCAGCTTTCACAGGTGA 545 SEQ ID NO: 332 -15.6 -25.4 74.5 -7.9 -1.9 -6.7

GTCAATTTGGCAGTTCTGGT 617 SEQ ID NO: 333 -15.6 -24.5 73.5 -8.9 0 -5.8

CATTCCAACACTTAGACATT 677 SEQ ID NO: 334 -15.6 -20.6 61.3 -5 0 -1.9

TGCTTCAGGGCCCTGTCTCT 763 SEQ ID NO: 335 -15.6 -30.8 87.2 -11.7 -0.7 -15.2

AGGGACTTCTGTCATAGTCT 942 SEQ ID NO: 336 -15.6 -24 73.7 -6.3 -2.1 -7.3

GAGAAGAGAGTTTGATCTGC 1288 SEQ ID NO: 337 -15.6 -20.8 64.3 -5.2 0 -5

CTTCCTTTCCATGTACCACT 1425 SEQ ID NO: 338 -15.6 -26.5 74.8 -10.9 0 -4.3

TCAAGGTTTTTGACATCTAA 1618 SEQ ID NO: 339 -15.6 -19 59.2 -2.3 -1 -4.5

TGGCCCGGATTTCGGGTAGT 1749 SEQ ID NO: 340 -15.6 -29.5 79.1 -9.8 -4.1 -11.8

CCAACTCTTGAGGATGTTCA 2955 SEQ ID NO: 341 -15.6 -23.3 68.2 -6.8 -0.7 -5.2

ATTTTGGACTGTTCGCTTAA 572 SEQ ID NO: 342 -15.5 -21.5 64 -5.5 -0.1 -3.3

CAGTTCTGGTTTTCTATACA 607 SEQ ID NO: 343 -15.5 -21.6 67 -6.1 0 -4.1

CTTATTCCTTCCTCCACGCA 725 SEQ ID NO: 344 -15.5 -28.1 76.7 -12.6 0 -3.6

GAGGGCTTTTTTCTGTTGCT 779 SEQ ID NO: 345 -15.5 -25.5 76.2 -9.5 -0.2 -3.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AGAGTTTGATCTGCCATTTT 1282 SEQ ID NO: 346 -15.5 -22.7 68.2 -7.2 0 -4.9

GGCTCCGGCTTGTGATGCTA

1490 SEQ ID NO: 347 -15.5 -29.3 80.8 -12.4 -1. 3 -6.3

ATCTTTAAAGCAAGTTTTTA

1983 SEQ ID NO: 348 -15.5 -16.9 54.6 -0.8 0 -7.7 TATCTTTAAAGCAAGTTTTT

1984 SEQ ID NO: 349 -15.5 -16.9 54.6 -0.8 0 -7'.7 TCAATATCTTTAAAGCAAGT

1988 SEQ ID NO: 350 -15.5 -16.9 54 -0.8 0 -7.7

CTTGAGTCAATACATCACCT 2917 SEQ ID NO: 351 -15.5 -22 65.2 -6 -0. 2 -7.6

ATCCCAACTCTTGAGGATGT 2958 SEQ ID NO: 352 -15.5 -24.5 70.4 -6.8 -2. 2 -6.7

AGCAAGTCTTTCCCTGGACT 52 SEQ ID NO: 353 -15.4 -26.7 76.2 -10 -1. 2 -6.3

TTAAAAAATCCCTTGCAGCT

556 SEQ ID NO: 354 -15.4 -20.9 60.1 -5.5 0 -5.2 CTTAAAAAATCCCTTGCAGC

557 SEQ ID NO: 355 -15.4 -20.9 60.1 -5.5 , 0 -5.2 GCTTAAAAAATCCCTTGCAG

558 SEQ ID NO: 356 -15.4 -20.9 60.1 -5.5 0 -5.2 GTTCGCTTAAAAAATCCCTT

562 SEQ ID NO: 357 -15.4 -20.9 60 -5.5 0 -3.1 AGGGGTCTGGGTACTCAGAC

1053 SEQ ID NO: 358 -15.4 -26.4 78.6 -7 -3. 8 -15.4

CGGATTTCGGGTAGTCGAAG 1744 SEQ ID NO: 359 -15.4 -23.6 66.6 -6.5 -1. 7 -4.3

CATACTGATGGCCCGGATTT 1757 SEQ ID NO: 360 -15.4 -25.9 70.6 -10.5 0 -6.6

GGTATTCTTCAGCCTGCATA 1773 SEQ ID NO: 361 -15.4 -25.6 75.1 -10.2 0 -4.9

TGTAACTTATGCTCTTTTGG 1856 SEQ ID NO: 362 -15.4 -20.6 63.2 -5.2 0 -3.6

TTCTTCTTCCCCCTCCCCAC 1919 SEQ ID NO: 363 -15.4 -33.5 87.7 -18.1 0 0

ATATCTTTAAAGCAAGTTTT

1985 SEQ ID NO: 364 -15.4 -16.8 54.3 -0.8 0 -7.7 TTCTGTCCGTTTTTCTTCTG

2168 SEQ ID NO: 365 -15.4 -24.1 72.3 -8.7 0 -2.6

CATTAGTACAGATTCGGTGA 2392 SEQ ID NO: 366 -15.4 -21.2 63.9 -5.8 0 -4.5

ATTTTGTTTCCAACTACTTA 2858 SEQ ID NO: 367 -15.4 -19.8 61 -3.9 -0. 2 -2.6

GAGTCAATACATCACCTCAT

2914 SEQ ID NO: 368 -15.4 -22.1 65.7 -6 -0. 4 -4.1 TGAGTCAATACATCACCTCA

2915 SEQ ID NO: 369 -15.4 -22.1 65.6 -6 -0. 4 -5.4 TTGTCAAATTTCGTGGCCTT

157 SEQ ID NO: 370 -15.3 -23.6 67.7 -8.3 0 -7.2

AGCCCAGCACCAATAGGTGT 298 SEQ ID NO: 371 -15.3 -28.5 78 -9.9 -3. 3 -9.7

ATCCCTTGCAGCTTTCACAG 549 SEQ ID NO: 372 -15.3 -26.8 76.2 -11.5 0 -5.8

TGTTCGCTTAAAAAATCCCT-

563 SEQ ID NO: 373 -15.3 -20.8 59.6 -5.5 0 -2.7 CTGTTCGCTTAAAAAATCCC

564 SEQ ID NO: 374 -15.3 -20.8 59.6 -5.5 0 -3.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTTTGGACTGTTCGCTTAAA 571 SEQ ID NO: 375 -15.3 -20.8 61.9 -5.5 0.7 -4

CTGTGTTTTGTCAATTTGGC 626 SEQ ID NO: 376 -15.3 -22.4 67.9 -7.1 0 -5

GACTTCTGTCATAGTCTGTA 939 SEQ ID NO: 377 -15.3 -22.5 70.5 -5.8 -1.3 -6.4

ACTCATGAGGTTGTTGAGGG 1511 SEQ ID NO: 378 -15.3 -23.6 70.9 -6.7 -1.5 -10.4

TGACTCATGAGGTTGTTGAG 1513 SEQ ID NO: 379 -15.3 -21.8 66.6 -5 -1.1 -10.4

ACTAACTCCTGTGCATGACT 1528 SEQ ID NO: 380 -15.3 -23.9 69.2 -8.6 0 -5.4

GAGGTATTCTTCAGCCTGCA 1775 SEQ ID NO: 381 -15.3 -26.5 77.5 -10.3 -0.8 -5.3

CTTCCCCCTCCCCACTCCCC 1914 SEQ ID NO: 382 -15.3 -38.9 94.1 -23.6 0 0

TATATGGAATCCTCTGGGGC

2097 SEQ ID NO: 383 -15.3 -24.5 70.5 -8.6 -0.3 -5.7 TTATATGGAATCCTCTGGGG

2098 SEQ ID NO: 384 -15.3 -22.8 66.7 -6.9 -0.3 -6.4 ATTAATAAGATTAGTTCCTA

2230 SEQ ID NO: 385 -15.3 -16.8 54.3 -1.4 0 -3.8

AATACATCACCTCATCCTTT 2909 SEQ ID NO: 386 -15.3 -22.7 66.1 -7.4 0 -1.2

ACCGCTTTTGCTATTTTGTT 3327 SEQ ID NO: 387 -15.3 -24 69.4 -7.1 -1.5 -5

CCCGTTTTTGATTTTAGTGT 3416 SEQ ID NO: 388 -15.3 -23.4 68.3 -8.1 0 -2.6

TGTCAAATTTCGTGGCCTTG 156 .SEQ ID NO: 389 -15.2 -23.5 67.3 -8.3 0 -7.2

TTGAGACACTTGCATGTTTT 434 SEQ ID NO: 390 -15.2 -21.4 64.8 -6.2 0.5 -6.6

CAGCTTTCACAGGTGAGGAG 541 SEQ ID NO: 391 -15.2 -24.4 72.5 -7.9 -1.2 -7.1

GTTTTCTATACATGTGTACC 599 SEQ ID NO: 392 -15.2 -21.4 65.9 -6.2 0 -6.7

TGTCAATTTGGCAGTTCTGG 618 SEQ ID NO: 393 -15.2 -23.3 69.7 -7.4 -0.4 -7.1

CATTGGCCCAAACTTATTCC 737 SEQ ID NO: 394 -15.2 -24.5 67.8 -9.3 0 -6.6

ATGGGGGATGTTACAAAGGG 958 SEQ ID NO: 395 -15.2 -22.3 64.8 -7.1 0 -3.1

TTGCTGGAGAGCTCGTCTGG 1122 SEQ ID NO: 396 -15.2 -26.8 77.2 -9.6 -2 -9.3

CAATATCTTTAAAGCAAGTT 1987 SEQ ID NO: 397 -15.2 -16.6 53.1 -0.8 0 -7.7

AAGATTAGTTCCTAAATTTC 2224 SEQ ID NO: 398 -15.2 -17.2 55.1 -1.4 -0.2 -4.9

GCCTTCAAAGGAAGAGGGAG 2351 SEQ ID NO: 399 -15.2 -23.2 66.7 -6 -2 -7

CACAGGTCCATTAGTACAGA 2400 SEQ ID NO: 400 -15.2 -23.3 69.2 -8.1 0 -5.3

TTTTGTTTCCAACTACTTAG 2857 SEQ ID NO: 401 -15.2 -19.8 61.2 -3.9 -0.5 -3.2

AGTCAATACATCACCTCATC 2913 SEQ ID NO: 402 -15.2 -21.9 65.9 -6 -0.4 -2.8

TTAAGGAAATTACCGCTTTT 3338 SEQ ID NO: 403 -15.2 -19.3 57.5 -3.4 -0.5 -3.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CGTGTCGGTCCGGAAGCCCA 312 SEQ ID NO: 404 -15.1 -31.6 80.5 -15.5 -0.7 -9.3

TAGTCTGTAGGAGGCAAGGC 928 SEQ ID NO: 405 -15.1 -24.9 74.4 -9 -0.6 -4.5

CTCATGAGGTTGTTGAGGGT 1510 SEQ ID NO: 406 -15.1 -24.6 73.9 -8.6 -0.6 -8.9

CTCTGTCTGCTGCGGGTAGT 1706 SEQ ID NO: 407 -15.1 -28.5 82.6 -13.4 0 -7

CTGTTCTTCTTCCCCCTCCC 1922 SEQ ID NO: 408 -15.1 -32.7 88.1 -17.6 0 0

AATATCTTTAAAGCAAGTTT 1986 SEQ ID NO: 409 -15.1 -16 52.1 -0.8 0 -7.1

CACATTTCAGCAACAGTAGC 2693 SEQ ID NO: 410 -15.1 -22.3 66.5 -7.2 0 -4.1

CTACTTAGAACTGTGACTAT 2845 SEQ ID NO: 411 -15.1 -19.1 59.4 -4 0 -3.6

GCCCAGCACCAATAGGTGTA 297 SEQ ID NO: 412 -15 -28.2 77.1 ^' -9.9 -3.3 -8.7

CTTTGGGCAGCATGACAAGG 357 SEQ ID NO: 413 -15 -24.5 69.9 -8.4 -1 -5.3

CCCTTGCAGCTTTCACAGGT 547 SEQ ID NO: 414 -15 -28.8 80.7 -13.8 0 -6.6

TATTATTTTGGACTGTTCGC 576 SEQ ID NO: 415 -15 -21 63.6 -5.5 -0.1 -4

AGGTTGTTGAGGGTGGCTCC 1504 SEQ ID NO: 416 -15 -28.3 82.8 -12 -1.2 -4

AGGTATTCTTCAGCCTGCAT 1774 SEQ ID NO: 417 -15 -25.9 76 -10.3 -0.3 -5.1

ACTTATGCTCTTTTGGCATG 1852 SEQ ID NO: 418 -15 -22.9 68.3 -5.8 -2.1 -6.2

GTTCCTAAATTTCTTCATAG 2217 SEQ ID NO: 419 -15 -19.3 60.2 -4.3 0 -4.9

TAAGATTAGTTCCTAAATTT 2225 SEQ ID NO: 420 -15 -16.5 53.3 -1.4 0.3 -4.5

GATGCATTCTTGAGAATTGT 2311 SEQ ID NO: 421 -15 -20.4 62.3 -5.4 0 -7.4

TCTTCCTTTCCCCTTTGGGG 3033 SEQ ID NO: 422 -15 -30 82.4 -12.4 -2.6 -8.9

TCTATACATGTGTACCTTTT

595 SEQ ID NO: 423 -14.9 -21.1 64.6 -6.2 0 -6.7 TTCTATACATGTGTACCTTT

596 SEQ ID NO: 424 -14.9 -21.1 64.6 -6.2 0 -6.7 TTTCTATACATGTGTACCTT

597 SEQ ID NO: 425 -14.9 -21.1 64.6 -6.2 0 -6.7 TTTTCTATACATGTGTACCT

598 SEQ ID NO: 426 -14.9 -21.1 64.6 -6.2 0 -6.6 GCTGGTATAGGGGTCTGGGT

1061 SEQ ID NO: 427 -14.9 -28.2 83 -13.3 0 -2.8

GGTGCTCAGCTTTTCGTGCT 1247 SEQ ID NO: 428 -14.9 -28.3 81.8 -12.7 -0.5 -4.6

GGATTTCGGGTAGTCGAAGA 1743 SEQ ID NO: 429 -14.9 -23.4 67.7 -6.5 -2 -4.6

CCCCTCCCCACTCCCCCAAT 1910 SEQ ID NO: 430 -14.9 -37.5 88.5 -22.6 0 -0.9

GCTTTGATTCACAGTTTGCA 2071 SEQ ID NO: 431 -14.9 -23.5 70.2 -8.6 0 -4.8

AATTAATAAGATTAGTTCCT 2231 SEQ ID NO: 432 -14.9 -16.4 53 -1.4 0 -4.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ATTAGTACAGATTCGGTGAC 2391 SEQ ID NO: 433 -14.9 -20.7 63.2 -5.8 0 -5.3

TTGTTTCCAACTACTTAGAA 2855 SEQ ID NO: 434 -14.9 -19.5 59.8 -3.9 -0.5 -3.3

TCACCATTTCCATCCCAACT 2969 SEQ ID NO: 435 -14.9 -26.8 73 -11.9 0 -1

CCTTTCCCCTTTGGGGAAGA 3029 SEQ ID NO: 436 -14.9 -28.7 77.1 -9 -4.8 -13.3

TACCGCTTTTGCTATTTTGT 3328 SEQ ID NO: 437 -14.9 -23.6 68. ≤ -7.1 -1.5 -5.1

TACAAGCAAGTCTTTCCCTG 56 SEQ ID NO: 438 -14.8 -23.7 68.5 -8.9 0 -3.3

CTTTCCATGTACCACTTGTC 1421 SEQ ID NO: 439 -14.8 -24.8 72.5 -10 0 -4.2

TTCCTTTCCATGTACCACTT 1424 SEQ ID NO: 440 -14.8 -25.7 73.3 -10.9 0 -4.3

GTGTAGTCCAGCAGGGCGGC 1678 SEQ ID NO: 441 -14.8 -30.9 86.8 -15 -1 ^• -6.1

TTCTTCAGCCTGCATACTGA 1769 SEQ ID NO: 442 -14.8 -25.2 73.3 -9.1 -1.2 -9.2

AACTTATGCTCTTTTGGCAT 1853 SEQ ID NO: 443 -14.8 -22.2 66.1 -5.8 -1.6 -5.5

GTATTTGATTATTATGCCTT 2015 SEQ ID NO: 444 -14.8 -20.1 61.8 -5.3 0 -3

TTTATATGGAATCCTCTGGG 2099 SEQ ID NO: 445 -14.8 -21.7 64.5 -6.9 0 -6.4

TAGTACAGATTCGGTGACCA 2389 SEQ ID NO: 446 -14.8 -23.3 67.9 -8.5 0 -5.3

AATTTTGTTTCCAACTACTT 2859 SEQ ID NO: 447 -14.8 -19.4 59.5 -3.9 -0.5 -3.8

TTGAGTCAATACATCACCTC 2916 SEQ ID NO: 448 -14.8 -21.5 64.8 -6 -0.4 -7.3

CCGCTTTTGCTATTTTGTTA 3326 SEQ ID NO: 449 -14.8 -23.5 68.2 -7.1 -1.5 -3.6

GTAACCCTTAGTGAAAGTTA 115 SEQ ID NO: 450 -14.7 -20.5 61.5 -5.3 -0.2 -4.6

TTGCAGCTTTCACAGGTGAG 544 SEQ ID NO: 451 -14.7 -24.5 72.8 -7.9 -1.9 -7.1

TCCAACACTTAGACATTTTT

674 SEQ ID NO: 452 -14.7 -20.1 60.8 -5.4 0 -1.9 TTCCAACACTTAGACATTTT

675 SEQ ID NO: 453 -14.7 -20.1 60.8 -5.4 0 -1.9 TCCTCCACGCATTCGGTCGG

716 SEQ ID NO: 454 -14.7 -30 78.7 -14.4 -0.8 -4.3

GTCTGTAGGAGGCAAGGCAG 926 SEQ ID NO: 455 -14.7 -25.9 76.2 -10.3 -0.7 -4.1

ATAAGCCCAAAGGTGCTCAG 1258 SEQ ID NO: 456 -14.7 -24.3 68.4 -8 -i.5 -6.7

TCCTTTCCATGTACCACTTG 1423 SEQ ID NO: 457 -14.7 -25.6 72.7 -10.9 0 -4.3

GATCCTTCCTTTCCATGTAC 1429 SEQ ID NO: 458 -14.7 -25.7 74.2 -11 0 -4.3

ATGTCTTTTATATGGAATCC 2105 SEQ ID NO: 459 -14.7 -19.7 60.8 -5 0 -5.4

GACAAAACAACCCTCAGAAC 2541 SEQ ID NO: 460 . -14.7 -19.9 57.6 -5.2 0 -2.5

ACTTAGAACTGTGACTATTT 2843 SEQ ID NO: 461 -14.7 -18.7 58.7 -4 0 -3.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AAAATCACCATTTCCATCCC 2973 SEQ ID NO: 462 -14.7 -23.6 65.4 -8.2 -0.4 -2.8

AAATGAGATTCCCGTTTTTG 3426 SEQ ID NO: 463 -14.7 -20.7 60.6 -6 0 -2.6

GCATGACAAGGCGACCGCGG 348 SEQ ID NO: 464 -14.6 -28.5 72.9 -12.3 -0.7 -11

GCTTTCACAGGTGAGGAGCC 539 SEQ ID NO: 465 -14.6 -27.5 79.4 -12.3 -0.3 -7J9

ATTCCAACACTTAGACATTT 676 SEQ ID NO: 466 -14.6 -20 60.5 -5.4 0 -1.9

AAGGCAGCATGGTTCAGAGG 913 SEQ ID NO: 467 -14.6 -24.9 72.7 -9.8 -0.2 -5.3

GGGTCTGGGTACTCAGACTT

1051 SEQ ID NO: 468 -14.6 -26.2 78 -7 -4.6 -16.3

TATGGAATAGTCCACTTGTT

1469 SEQ ID NO: 469 -14.6 -21.3 64.3 -4.3 -2.4 -9.7 TTATGGAATAGTCCACTTGT

1470 SEQ ID NO: 470 -14.6 -21.3 64.3 -4.3 -2.4 -9.7 CGGCTTGTGATGCTATTATG

1485 SEQ ID NO: 471 -14.6 -22.8 66.4 -7.5 ' -0.5 -4.5

TTAATAAGATTAGTTCCTAA 2229 SEQ ID NO: 472 -14.6 -16.1 52.4 -1.4 0 -3.2

ATGGAGCATTTGCTTTGAAA 2646 SEQ ID NO: 473 -14.6 -20.6 61.5 -5 -0.9 -8.5

CCCCTTTGGGGAAGATTTGA 3024 SEQ ID NO: 474 -14.6 -26 71.4 -9 -2.4 -8.5

CCTTGGGAAGGACACATCAG 141 SEQ ID NO: 475 -14.5 -24 68.4 -8.3 -1.1 -4.9

TCCGGAAGCCCAGCACCAAT 304 SEQ ID NO: 476 -14.5 -29.5 75.5 -13.7 -1.2 -9.5

TAAAAAATCCCTTGCAGCTT 555 SEQ ID NO: 477 -14.5 -20.9 60.1 -6.4 0 -5.2

TTTTTTCTGTTGCTTCAGGG 773 SEQ ID NO: 478 -14.5 -23.4 71.3 -8.2 -0.5 -6

GGCTTCTAGCTTAAGTCCAT 809 SEQ ID NO: 479 -14.5 -25.1 73.9 -8.9 -1.7 -8.6

TGGGGGATGTTACAAAGGGA 957 SEQ ID NO: 480 -14.5 -22.9 66.1 -8.4 0 -3.1

GCTGGAGAGCTCGTCTGGTA 1120 SEQ ID NO: 481 -14.5 -27.6 80.1 -11.7 -1.3 -9.3

CATGTACCACTTGTCGGTAA 1416 SEQ ID NO: 482 -14.5 -23.5 67.6 -7.8 -1.1 -6.5

TCCACTTGTTGCCCAGTAAC 1459 SEQ ID NO: 483 -14.5 -26.5 74.3 -11.5 -0.1 -3.5

TCTTCAGCCTGCATACTGAT 1768 SEQ ID NO: 484 -14.5 -25.1 72.9 -9.1 -1.4 -9.5

TTTTGGCATGCAACATTTCA 1842 SEQ ID NO: 485 -14.5 -22 64.8 -6.6 -0.5 -9.3

CTATTAGTATTTGATTATTA 2021 SEQ ID NO: 486 -14.5 -15.7 52.6 -1.1 0 -2

ATATGGAATCCTCTGGGGCT 2096 SEQ ID NO: 487 -14.5 -25.7 73 -10.6 -0.3 -6.4

CTGTAAGCTCAAATCCCCCG 2263 SEQ ID NO: 488 -14.5 -26.7 70.7 -12.2 0 -4.5

AGAATTTCCTATTAGCTGTT 2492 SEQ ID NO: 489 -14.5 -20.9 63.9 -6.4 0 -4.8

ACTACTTAGAACTGTGACTA 2846 SEQ ID NO: 490 -14.5 -19.3 60 -4.8 0 -3.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TGTGTTTTGTCAATTTGGCA 625 SEQ ID NO: 491 -14.4 -22.2 67.1 -7.1 -0.4 -7.2

TCATTCCAACACTTAGACAT 678 SEQ ID NO: 492 -14.4 -20.9 62.4 -6.5 0 -2.4

CACGCATTCGGTCGGCCCTT 711 SEQ ID NO: 493 -14.4 -31.1 79.8 -15.8 -0.8 -7.5

TTTTTCTGTTGCTTCAGGGC 772 SEQ ID NO: 494 -14.4 -25.1 75.6 -10.1 -0.3 -7

CTGTAGGAGGCAAGGCAGCA 924 SEQ ID NO: 495 -14.4 -26.8 76.5^" -11.4 -0.9 -5.3

GGGATGTTACAAAGGGACTT 954 SEQ ID NO: 496 -14.4 -21.7 64 -5.8 -1.4 -5.7

GGAGAGCTCGTCTGGTAACT 1117 SEQ ID NO: 497 -14.4 -25.3 73.7 -10 -0.3 -9.3

GTTTTCAAGGTTTTTGACAT 1622 SEQ ID NO: 498 -14.4 -20.2 62.7 -4.4 -1.3 -4.8

TGTGTAGTCCAGCAGGGCGG 1679 SEQ ID NO: 499 -14.4 -29.1 81.9 -12.9 -1.8 ^• -6.9

ATGGCCCGGATTTCGGGTAG 1750 SEQ ID NO: 500 -14.4 -28.3 75.8 -9.8 -4.1 -11.8

TATGCTCTTTTGGCATGCAA 1849 SEQ ID NO: 501 -14.4 -23.5 68.5 -7 -2.1 -10.1

TTTTCTTCCTGTTCTTCTTC 1930 SEQ ID NO: 502 -14.4 -23.5 73.2 -9.1 0 0

TTCAATATCTTTAAAGCAAG

1989 SEQ ID NO: 503 -14.4 -15.8 51.5 -0.8 0 -7.7 ATTCAATATCTTTAAAGCAA

1990 ' , SEQ ID NO: 504 -14.4 -15.8 51.4 -0.8 0 -7.7 AATTCAATATCTTTAAAGCA

1991 .SEQ ID NO: 505 -14.4 -15.8 51.4 -0.8 0 -7.7 TATTAGTATTTGATTATTAT

2020 SEQ ID NO: 506 -14.4 -14.8 50.6 0 0 -1.4

ATAAGATTAGTTCCTAAATT 2226 SEQ ID NO: 507 -14.4 -16.4 53 -1.4 -0.2 -3.5

CCTGTAAGCTtOAAATCCCCC 2264 SEQ ID NO: 508 -14.4 -27.9 74 -13.5 0 -5

CAGGTCCATTAGTACAGATT 2398 SEQ ID NO: 509 -14.4 -22.5 67.7 -8.1 0 -5.3

CCTCATCCTTTCCTTTCTCT 2900 SEQ ID NO: 510 -14.4 -27.6 79.4 -13.2 0 -0.5

AAAATCCCTTGCAGCTTTCA 552 SEQ ID NO: 511 -14.3 -23.8 67.3 -9.5 0 -5.2

GCTCAGCTTTTCGTGCTTGC 1244 SEQ ID NO: 512 -14.3 -27.8 80.4 -12.7 -0.6 -5.9

GCTTGTGATGCTATTATGGA 1483 SEQ ID NO: 513 -14.3 -22.6 67.5 -8.3 0 -3.6

GAGGGTGGCTCCGGCTTGTG 1496 SEQ ID NO: 514 -14.3 -30.5 84.2 -14.8 -1.3 -6.6

TAGTCCAGCAGGGCGGCATT 1675 SEQ ID NO: 515 -14.3 -29.3 81 -13.2 -1.8 -6.9

TTGTAACTTATGCTCTTTTG 1857 SEQ ID NO: 516 -14.3 -19.5 60.9 -5.2 0 -3.6

GGGCCTTCAAAGGAAGAGGG 2353 SEQ ID NO: 517 -14.3 -25 70.1 -8.7 -2 -8.6

CAGAGGTGCTCGGGCCTTCA 2364 SEQ ID NO: 518 -14.3 -29.9 82.6 -14.1 -1.4 -8.5

TACTTAGAACTGTGACTATT 2844 SEQ ID NO: 519 -14.3 -18.3 57.8 -4 0 -3.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTACCGCTTTTGCTATTTTG 3329 SEQ ID NO: 520 -14.3 -22.5 65.6 -7.1 -1 -3.6

TCTTGTAAATCCCCAGTATC 259 SEQ ID NO: 521 -14.2 -23.3 67.8 -9.1 0 -1.8

TTCGCTTAAAAAATCCCTTG 561 SEQ ID NO: 522 -14.2 -19.7 57.3 -5.5 0 -3.1

CTATACATGTGTACCTTTTA 594 SEQ ID NO: 523 -14.2 -20.4 62.5 -6.2 0 -6:7

CTTCTAGCTTCATTCCAACA 687 SEQ ID NO: 524 -14.2 -23.3 68.7 -9.1 0 -4.3

CTTTTTTCTGTTGCTTCAGG 774 SEQ ID NO: 525 -14.2 -23.1 70.6 -8.2 -0.5 -6

AGCATGGTTCAGAGGTAGGC 908 SEQ ID NO: 526 -14.2 -25.8 77.2 -11.6 0 -5

AAGGGACTTCTGTCATAGTC 943 SEQ ID NO: 527 -14.2 -22.4 69 -6.1 -2.1 -7.2

TGGACTTGAGGCTCATCTGG 1180 SEQ ID NO: 528 -14.2 -25.1 73.4 -10.9 0 -5

TTCCCCCTCCCCACTCCCCC 1913 SEQ ID NO: 529 -14.2 -40 95.3 -25.8 0 0

TCTTTAAAGCAAGTTTTTAA

1982 SEQ ID NO: 530 -14.2 -16.2 52.8 -1.4 -0.2 -7.7

TTTGATTATTATGCCTTTTT

2012 SEQ ID NO: 531 -14.2 -19.5 60.3 -5.3 0 -3 AGCTTTGATTCACAGTTTGC

2072 SEQ ID NO: 532 -14.2 -22.8 69.3 -8.6 0 -4.3

CATGGAGGAATCCTGTAAGC 2275 SEQ ID NO: 533 -14.2 -22.9 66.5 -5.9 -2.8 -7.8

TCCTTTCCTTTCTCTTTGCA 2895 SEQ ID NO: 534 -14.2 -26.3 77.1 -12.1 0 -4.8

ATAGAATAATTAAGTACTGT 3388 SEQ ID NO: 535 -14.2 -14.9 50 -0.5 0 -6.3

TTTGTCAATTTGGCAGTTCT 620 SEQ ID NO: 536 -14.1 -22.3 67.9 -7.4 -0.6 -7.6

GTTTTGTCAATTTGGCAGTT 622 SEQ ID NO: 537 -14.1 -22.3 68 -7.4 -0.6 -7.6

CGCATTCGGTCGGCCCTTAC 709 SEQ ID NO: 538 -14.1 -30.1 78.4 -15.5 -0.2 -7.2

GCTTCTAGCTTAAGTCCATT 808 SEQ ID NO: 539 -14.1 -24 71.6 -8.9 -0.9 -6.1

AAGTTCCAGTATCAGATGTG 1148 SEQ ID NO: 540 -14.1 -21.5 65.8 -7.4 0 -3.6

AGGTGCTCAGCTTTTCGTGC 1248 SEQ ID NO: 541 -14.1 -27.4 80.1 -12.7 -0.3 -5.7

CTTCAGCCTGCATACTGATG 1767 SEQ ID NO: 542 -14.1 -24.7 71.1 -9.1 -1.4 -9.5

TTTTTCTTCCTGTTCTTCTT 1931 SEQ ID NO: 543 -14.1 -23.2 71.8 -9.1 0 0

ATTTGATTATTATGCCTTTT

2013 SEQ ID NO: 544 -14.1 -19.4 59.9 -5.3 0 -3 GCTATTAGTATTTGATTATT

2022 SEQ ID NO: 545 -1.4.1 -17.8 57.5 -3.7 0 -3.3

AAGAACCGTTCTGTCCGTTT 2176 SEQ ID NO: 546 -14.1 -24.6 68.8 -9.5 -0.9 -8.9

ACATTTCAGCAACAGTAGCA- 2692 SEQ ID NO: 547 -14:1 -22.3 66.5 -7.2 -0.9 -4.5

TCACCTCATCCTTTCCTTTC 2903 SEQ ID NO: 548 -14.1 -26.7 77.1 -12.6 0 -0.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TGTCCTCCCATATTTGTTCT 3096 SEQ ID NO: 549 -14.1 -26.1 75.5 -12 0 -2.1 ATTCATAAAGTTACAAGCAA 67 SEQ ID NO: 550 -14 -16.5 52.7 -2.5 0 -4.1

TCAGACTACAGTAACCCTTA 125 SEQ ID NO: 551 -14 -22.5 66.1 -8.5 0 -3.6

AAATTATAGGCAGTTCTTTG 216 SEQ ID NO: 552 -14 -18.6 58.4 -4.6 0 -4

TTTGGACTGTTCGCTTAAAA 570 SEQ ID NO: 553 -14 -20 59.7 -5.5 -0.1 -4

TTGTCAATTTGGCAGTTCTG 619 SEQ ID NO: 554 -14 -22.2 67.4 -7.4 -0.6 -7.6

CACTCCAGCAGTTCTGAAGC 1374 SEQ ID NO: 555 -14 -25.7 74.5 -11 -0.4 -5.2

CGGCATTGACTTGTTCCTGG 1662 SEQ ID NO: 556 -14 -26.2 73.2 -12.2 0 -4.7

GGTGCTCGGGCCTTCAAAGG 2360 SEQ ID NO: 557 -14 -28.4 77.4 -13.5 -0.8 -7.8

CTCTTCCTTTCCCCTTTGGG 3034 SEQ ID NO: 558 -14 -29.7 81.8 -14.1 -1.5 -5.1

TCCCTTGCAGCTTTCACAGG 548 SEQ ID NO: 559 -13.9 -28 78.9 -14.1 0 -6.2

GTTCTGGTTTTCTATACATG 605 SEQ ID NO: 560 -13.9 -20.9 65.3 -7 0 -4.7

TGTAGGAGGCAAGGCAGCAT 923 SEQ ID NO: 561 -13.9 -25.9 74.4 -11 -0.9 -5.3

GGTGAGCTGGTATAGGGGTC 1066 SEQ ID NO: 562 -13.9 -26.7 79.8 -12.8 0 -5

CAGTATCAGATGTGGGATGC 1142 SEQ ID NO: 563 -13.9 -23.3 69.7 -9.4 0 -4.2

CCTGCATACTGATGGCCCGG 1761 SEQ ID NO: 564 -13.9 -29.8 77.5 -15.1 -0.6 -6.9

CCATTAGTACAGATTCGGTG 2393 SEQ ID NO: 565 -13.9 -22.6 66.3 -8.7 0 -5.3

CATTTCAGCAACAGTAGCAG 2691 SEQ ID NO: 566 -13.9 -22.1 66.2 -7.2 -0.9 -4.5

TAGAATAATTAAGTACTGTT 3387 SEQ ID NO: 567 -13.9 -15 50.3 -1 0 -6.3

CCGGAAGCCCAGCACCAATA 303 SEQ ID NO: 568 -13.8 -28.8 73.6 -13.7 -1.2 -6.3

ATTGAGACACTTGCATGTTT 435 SEQ ID NO: 569 -13.8 -21.3 64.4 -7 -0.1 -6.8

GGACAACGCTTTCTCTGTGT 640 SEQ ID NO: 570 -13.8 -24.9 72 -11.1 0 -3.5

AGCTTCATTCCAACACTTAG 682 SEQ ID NO: 571 -13.8 -22.2 66 -8.4 0 -4.3

GCTTCAGGGCCCTGTCTCTC 762 SEQ ID NO: 572 -13.8 -31.2 89.6 -13.6 -0.3 -15.8

TCTAGCTTAAGTCCATTGGC 805 SEQ ID NO: 573 -13.8 -24.2 71.7 -10.4 0 -6.9

ATGGCTTCTAGCTTAAGTCC 811 SEQ ID NO: 574 -13.8 -24.4 72.6 -8.9 -1.7 -7.8

GAGTTTGATCTGCCATTTTG 1281 SEQ ID NO: 575 -13.8 -22.7 67.8 -8.9 0 -4.9

GATGGATCCTTCCTTTCCAT 1433 SEQ ID NO: 576 -13.8 -26.4 74.6 -10.4 -2.2 -8.7

ATGACTCATGAGGTTGTTGA 1514 SEQ ID NO: 577 -13.8 -21.8 66.3 -6.8 0 -10.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GTTACACATTGTGTAGTCCA 1688 SEQ ID NO: 578 -13.8 -23.3 70.3 -7.4 -2 -11.4

CTGTCTGCTGCGGGTAGTTA 1704 SEQ ID NO: 579 -13.8 -27 78.3 -13.2 0 -7

TTTTGAAAGCAGAGCTCCTA 1881 SEQ ID NO: 580 -13.8 -22.3 65.8 -7.6 -0.8 -8.4

TTGTTTTGAAAGCAGAGCTC 1884 SEQ ID NO: 581 -13.8 -21 64 -6.3 -0.8 -8

TTGATTATTATGCCTTTTTA 2011 SEQ ID NO: 582 -13.8 -19.1 59.3 -5.3 0 -3

TCCATTACAATGTCTTTTAT 2114 SEQ ID NO: 583 -13.8 -19.6 60.4 -5.8 0 -5.1

GACTATTTGACATCCTAGCA 2831 SEQ ID NO: 584 -13.8 -22.6 66.8 -8.8 0 -4.1

CCTTTCCTTTCTCTTTGCAT 2894 SEQ ID NO: 585 -13.8 -25.9 75.2 -12.1 0 -5.1

ATTACCGCTTTTGCTATTTT 3330 SEQ ID NO: 586 -13.8 -22.5 65.7 -7.1 -1.5 -4.2 AGTCTTTCCCTGGACTCTGT 48 SEQ ID NO: 587 -13.7 -27.4 80.2 -12.6 -1 -4.8

GACAAGGCGACCGCGGGCGG 344 SEQ ID NO: 588 -13.7 -31 76.3 -15.3 -1.5 -12

TGAGACACTTGCATGTTTTC 433 SEQ ID NO: 589 -13.7 -21.7 66 -7.5 -0.1 -6.8

CCTTGCAGCTTTCACAGGTG 546 SEQ ID NO: 590 -13.7 -26.8 76.9 -12.2 -0.8 -6.5

ATACATGTGTACCTTTTATT 592 SEQ ID NO: 591 -13.7 -19.9 61.4 -6.2 0 -6.7

GCTTCATTCCAACACTTAGA 681 SEQ ID NO: 592 -13.7 -22.8 67.1 -9.1 0 -2.8

TGAGGGCTTTTTTCTGTTGC 780 SEQ ID NO: 593 -13.7 -24.6 73.8 -10.9 0 -3.5

AATGGGGGATGTTACAAAGG 959 SEQ ID NO: 594 -13.7 -20.4 60.4 -6.7 0 -3.1

GCCGTGAGGGGGCATTGTCA 983 SEQ ID NO: 595 -13.7 -30.1 82.5 -14.6 -1.8 -7.5

GTGCTCAGCTTTTCGTGCTT 1246 SEQ ID NO: 596 -13.7 -27.2 79.4 -12.7 -0.6 -4.7

GTTTTGCCACTAACTCCTGT 1536 SEQ ID NO: 597 -13.7 -25.7 73.6 -12 0 -2.7

AGTTTTCAAGGTTTTTGACA 1623 SEQ ID NO: 598 -13.7 -20.2 62.9 -5.4 -1 -4.6

TATTTGATTATTATGCCTTT 2014 SEQ ID NO: 599 -13.7 -19 59 -5.3 0 -3

TTTTATATGGAATCCTCTGG 2100 SEQ ID NO: 600 -13.7 -20.6 62.3 -6.9 0 -6.4

TAATTAATAAGATTAGTTCC 2232 SEQ ID NO: 601 -13.7 -15.2 50.5 -1.4 0 -4.7

TTACCATGGAGGAATCCTGT 2279 SEQ ID NO: 602 -13.7 -24.1 68.9 -7.6 -2.8 -8.9

CTTGAGAATTGTTTCAGTTC 2303 SEQ ID NO: 603 -13.7 -19.8 62.5 -5.4 -0.4 -3.7

ACAGGTCCATTAGTACAGAT 2399 SEQ ID NO: 604 -13.7 -22.6 68 -8.9 0 -5.3

GACACAGGTCCATTAGTACA• 2402 SEQ ID NO: 605 -13.7 -23.5 69.5 -9 -0.6 -6.5

ACCTCATCCTTTCCTTTCTC 2901 SEQ ID NO: 606 -13.7 -26.9 78 -13.2 0 -0.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CATCCCAACTCTTGAGGATG 2959 SEQ ID NO: 607 -13.7 -24 68.3 -6.8 -3.5 -9.3

ACTTTATTTTAAACAAATGT

3232 SEQ ID NO: 608 -13.7 -14.3 48.2 -0.3 0.1 -4.4

AATTCATAAAGTTACAAGCA

68 SEQ ID NO: 609 -13.6 -16.5 52.7 -2.9 0 -4.1

CAGACTACAGTAACCCTTAG 124 SEQ ID NO: 610 -13.6 -22.1 64.8 -8.5 0 -3.6

CTTGGGAAGGACACATCAGA 140 SEQ ID NO: 611 -13.6 -22.6 66.1 -8.3 -0.4 -2.9

TTCATTCCAACACTTAGACA 679 SEQ ID NO: 612 -13.6 -21 62.7 -7.4 0 -2.5

GCATTGTCATGCTAATGGGG 972 SEQ ID NO: 613 -13.6 -24.2 70.1 -8.3 -2.3 -8.3

TATTATGGAATAGTCCACTT 1472 SEQ ID NO: 614 -13.6 -19.8 60.6 -4.3 -1.9 -9.2

TGGCTCCGGCTTGTGATGCT 1491 SEQ ID NO: 615 -13.6 -29.6 81.1 -14.6 -1.3 -5.7

TTTTCAAGGTTTTTGACATC 1621 SEQ ID NO: 616 -13.6 -19.4 60.9 -4.4 -1.3 -4.8

TTTCGGGTAGTCGAAGAAGT 1740 SEQ ID NO: 617 -13.6 -22.1 65.1 -6.5 -2 -4.6

TAACTTATGCTCTTTTGGCA

1854 SEQ ID NO: 618 -13.6 -21.9 65.6 -7 -1.2 -4.8

TTTGTTTTGAAAGCAGAGCT

1885 SEQ ID NO: 619 -13.6 -20.7 62.9 -6.3 -0.6 -7.8 TTTTGTTTTGAAAGCAGAGC

1886 SEQ ID NO: 620 -13.6 -19.9 61.3 -6.3 0 -4.1 CCTGTTCTTCTTCCCCCTCC

1923 SEQ ID NO: 621 -13.6 -32.7 88.1 -19.1 0 0

GTTTTTAATTAGCGTTACTT 1970 SEQ ID NO: 622 -13.6 -19.2 59.8 -5.6 0 -4.1

GGTATCCATCTGTGAGTTCA 2140 SEQ ID NO: 623 -13.6 -24.7 74.3 -11.1 0 -3

AATAAGATTAGTTCCTAAAT 2227 SEQ ID NO: 624 -13.6 -15.6 50.9 -1.4 -0.2 -3.5

GTCCTCCCATATTTGTTCTA 3095 SEQ ID NO: 625 -13.6 -25.8 75.1 -12.2 0 -2.1

CCGTCTCCACTTTGGGCAGC 366 SEQ ID NO: 626 -13.5 -30.4 82.8 -15.9 -0.9 -5.7

AAAAAATCCCTTGCAGCTTT 554 SEQ ID NO: 627 -13.5 -21.3 60.9 -7.8 0 -5.2

ACTGTTCGCTTAAAAAATCC 565 SEQ ID NO: 628 -13.5 -19 56.7 -5.5 0 -3.1

TGTTTTGTCAATTTGGCAGT 623 SEQ ID NO: 629 -13.5 -22.2 67.5 -8.1 -0.3 -7.3

GGATGTTACAAAGGGACTTC 953 SEQ ID NO: 630 -13.5 -20.9 62.9 -5.8 -1.6 -5.9

TGGAGAGCTCGTCTGGTAAC 1118 SEQ ID NO: 631 -13.5 -24.4 71.5 -10 -0.3 -9.3

TCCAGTATCAGATGTGGGAT 1144 SEQ ID NO: 632 -13.5 -23.9 70.9 -9.8 -0.3 -5.9

CATAAGCCCAAAGGTGCTCA 1259 SEQ ID NO: 633 -13.5 -25 69.3 -9.9 -1.5 -6.7

TACCACTTGTCGGTAAATGT 1412 SEQ ID NO: 634 -13.5 -22.1 64.3 -7.8 -0.6 -5.7

TCTGTCCGTTTTTCTTCTGA 2167 SEQ ID NO: 635 -13.5 -24.6 73.3 -11.1 0 -2.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTCCTAAATTTCTTCATAGT 2216 SEQ ID NO: 636 -13.5 -19.3 60.2 -5.8 0 -4.6

GCTATGGAGCATTTGCTTTG 2649 SEQ ID NO: 637 -13.5 -23.8 70.1 -8.6 -1.7 -8.5

TCCTTTCCCCTTTGGGGAAG 3030 SEQ ID NO: 638 -13.5 -28.5 77.5 -10.2 -4.8 -13.3

GCTTTTGCTATTTTGTTATA 3324 SEQ ID NO: 639 -13.5 -20.4 63.5 -5.8 -1 -3'.7

GTTTTTGATTTTAGTGTCTC 3413 SEQ ID NO: 640 -13.5 -20.3 65.4 -6.8 0 -2.3

AAAGGGACTTCTGTCATAGT 944 SEQ ID NO: 641 -13.4 -21.3 64.9 -6.3 .-1.6 -5.7

GTTACAAAGGGACTTCTGTC 949 SEQ ID NO: 642 -13.4 -21.6 65.7 -5.8 -2.4 -7.1

AAAGTTCCAGTATCAGATGT 1149 SEQ ID NO: 643 -13.4 -20.8 63.6 -7.4 0 -3.6

CTCAGCTTTTCGTGCTTGCT 1243 SEQ ID NO: 644 -13.4 -26.9 77.8 -12.7 -0.6 -5.3

ATTATGGAATAGTCCACTTG 1471 SEQ ID NO: 645 -13.4 -20.1 61.1 -4.3 -2.4 -9.7

ATTGTGTAGTCCAGCAGGGC 1681 SEQ ID NO: 646 -13.4 -27.2 80.1 -12.9 -0.7 -5.6

CTGCTGCGGGTAGTTACACA 1700 SEQ ID NO: 647 -13.4 -26.3 74.6 -12.9 0 -7.3

CTTTTATATGGAATCCTCTG 2101 SEQ ID NO: 648 -13.4 -20.3 61.6 -6.9 0 -6.4

TGTCTTTTATATGGAATCCT 2104 SEQ ID NO: 649 -13.4 -20.6 62.8 -7.2 0 -6.4

CGGGCCTTCAAAGGAAGAGG 2354 SEQ ID NO: 650 -13.4 -24.6 67.8 -9.6 -1.5 -8.6

TAACCCTTAGTGAAAGTTAA 114 SEQ ID NO: 651 -13.3 -18.6 56.7 -5.3 0.3 -4.3

TTATTATTTTGGACTGTTCG 577 SEQ ID NO: 652 -13.3 -19.3 59.8 -5.5 -0.1 -4

TATACATGTGTACCTTTTAT 593 SEQ ID NO: 653 -13.3 -19.5 60.5 -6.2 0 -6.7

TTTTGTCAATTTGGCAGTTC 621 SEQ ID NO: 654 -13.3 -21.5 66.2 -7.4 -0.6 -7.6

TTCGGTCGGCCCTTACAGCT 705 SEQ ID NO: 655 -13.3 -30.2 80.9 -16.2 -0.4 -7.2

GCATTCGGTCGGCCCTTACA 708 SEQ ID NO: 656 -13.3 -30 79.7 -16.2 -0.2 -7.2

ACGCATTCGGTCGGCCCTTA 710 SEQ ID NO: 657 -13.3 -30.1 78.4 -15.9 -0.8 -7.5

CCACGCATTCGGTCGGCCCT 712 SEQ ID NO: 658 -13.3 -33 82.6 -18.8 -0.8 -7.5

CTTCTAGCTTAAGTCCATTG 807 SEQ ID NO: 659 -13.3 -22.2 67 -8.9 0 -6.1

TCATGCTAATGGGGGATGTT 966 SEQ ID NO: 660 -13.3 -23.5 68.6 -9.4 -0.6 -4.4

CTCTCGTTGATCAAACTGGA 1565 SEQ ID NO: 661 -13.3 -21.9 64.3 -7.9 -0.3 -8.7

TTGTGTAGTCCAGCAGGGCG 1680 SEQ ID NO: 662 -13.3 -28 79.6 -12.9 -1.8 -6.9

CGGGTAGTCGAAGAAGTAGC- 1737 SEQ ID NO: 663 -13.3 -23 66.7 -9.7 0:4 -5

TAATAAGATTAGTTCCTAAA 2228 SEQ ID NO: 664 -13.3 -15.3 50.4 -1.4 -0.2 -3.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TACCATGGAGGAATCCTGTA 2278 SEQ ID NO: 665 -13.3 -23.7 68 -7.6 -2.8 -8.9

GTGCTCGGGCCTTCAAAGGA 2359 SEQ ID NO: 666 -13.3 -27.8 76.2 -13.5 -0.8 -9.2

TCCCCTTTGGGGAAGATTTG 3025 SEQ ID NO: 667 -13.3 -25.8 71.7 -9 -3.5 -10.7

CTTCCTTTCCCCTTTGGGGA

3032 SEQ ID NO: 668 -13.3 -30.2 81.9 -13.3 -3.6 -10.9

GTCTTTCCCTGGACTCTGTA

47 SEQ ID NO: 669 -13.2 -27.1 79.1 -13.4 -0.2 -4.4

GCAAGTCTTTCCCTGGACTC 51 SEQ ID NO: 670 -13.2 -27.1 11.1 -12.4 -1.4 -6.5

TTGGACTGTTCGCTTAAAAA 569 SEQ ID NO: 671 -13.2 -19.2 57.5 -5.5 -0.1 -4

GCAGCATGGTTCAGAGGTAG 910 SEQ ID NO: 672 -13.2 -25.3 75.5 -11.6 -0.2 -5

TGTTACAAAGGGACTTCTGT 950 SEQ ID NO: 673 -13.2 -21.2 64 -5.8 -2.2 ^■ -6.9

GATGTTACAAAGGGACTTCT 952 SEQ ID NO: 674 -13.2 -20.6 62.3 -5.8 -1.6 -5.9

CATGCTAATGGGGGATGTTA 965 SEQ ID NO: 675 -13.2 -22.8 66.5 -9.6 0 -3.6

CTTGCTGGAGAGCTCGTCTG 1123 SEQ ID NO: 676 -13.2 -26.5 76.5 -11.3 -2 -9.3

CTGGACTTGAGGCTCATCTG 1181 SEQ ID NO: 677 -13.2 -24.8 72.8 -11.6 0 -5

GTAGTTACACATTGTGTAGT 1691 SEQ ID NO: 678 -13.2 -21.1 66.5 -6.1 -1.7 -11.1

ATTCTTCAGCCTGCATACTG 1770 SEQ ID NO: 679 -13.2 -24.6 71.9 -10.9 -0.2 -7.2

TGTAAGCTCAAATCCCCCGC 2262 SEQ ID NO: 680 -13.2 -27.6 72.7 -14.4 0 -5

GAATTTCCTATTAGCTGTTT 2491 SEQ ID NO: 681 -13.2 -21 64 -7.8 0 -4.8

ACAACCCTCAGAACATATTT 2535 SEQ ID NO: 682 -13.2 -21.1 61.5 -7.9 0 -2.5

CGAGACAAAACAACCCTCAG 2544 SEQ ID NO: 683 -13.2 -21.2 59.6 -7.3 -0.4 -3.9

AACTACTTAGAACTGTGACT 2847 SEQ ID NO: 684 -13.2 -18.9 58.5 -5.7 0 -3.3

CCAACTACTTAGAACTGTGA 2849 SEQ ID NO: 685 -13.2 -20.5 61.1 -7.3 0 -3.3

ACCTTGAGTCAATACATCAC

2919 SEQ ID NO: 686 -13.2 -21.3 63.8 -7.4 -0.4 -7.6

ACCTGTGGCATCGCATGTTA

3156 SEQ ID NO: 687 -13.2 -26.7 74.8 -12.6 -^•0.7 -5.3 TACCTGTGGCATCGCATGTT

3157 SEQ ID NO: 688 -13.2 -26.7 74.8 -12.6 -0.7 -5.3 GATTTTAGTGTCTCACGACA

3407 SEQ ID NO: 689 -13.2 -21.9 66.1 -6.8 -1.9 -8.4 AAGCCCAGCACCAATAGGTG

299 SEQ ID NO: 690 -13.1 -26.6 72.4 -10.5 -3 -9.2 GAAGCCCAGCACCAATAGGT

300 SEQ ID NO: 691 -13.1 -27.2 73.8 -13 -1 -5.2 TTTATTATTTTGGACTGTTC

578 SEQ ID NO: 692 -13.1 -18.6 59.5 -5.5 0 -3.4

GGCTCGGATGAGGGCTTTTT 788 SEQ ID NO: 693 -13.1 -27 76.4 -12.5 -1.3 -6.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTCTAGCTTAAGTCCATTGG 806 SEQ ID NO: 694 -13.1 -22.5 67.6 -8.9 0 -7.8

CAAAGGTGCTCAGCTTTTCG 1251 SEQ ID NO: 695 -13.1 -23.7 68.4 -9.9 -0.5 -3.8

AGAAGAGAGTTTGATCTGCC 1287 SEQ ID NO: 696 -13.1 -22.2 66.8 -9.1 0 -5

GTACCACTTGTCGGTAAATG 1413 SEQ ID NO: 697 -13.1 -22.1 64.3 -7.8 -1.1 -615

TTTGCCACTAACTCCTGTGC 1534 SEQ ID NO: 698 -13.1 -26.2 74 -13.1 0.2 -4

AGTTACACATTGTGTAGTCC 1689 SEQ ID NO: 699 -13.1 -22.6 69.4 -7.4 -2 -11.4

TCTGCTGCGGGTAGTTACAC 1701 SEQ ID NO: 700 -13.1 -26 75.2 -12.9 0 -7.3

ATTATGCCTTTTTAAATTCA 2005 SEQ ID NO: 701 -13.1 -18.4 57 -5.3 0 -4.5

CTCCATTACAATGTCTTTTA 2115 SEQ ID NO: 702 -13.1 -20.5 62.4 -7.4 0 -5.1

GTGTTGGTATCCATCTGTGA 2145 SEQ ID NO: 703 -13.1 -24.8 74.3 -11 -0.4 -4.4

ATCACCATTTCCATCCCAAC 2970 SEQ ID NO: 704 -13.1 -25.9 71.1 -12.8 0 -1

TAAAGACTCTTGTAAATCCC 266 SEQ ID NO: 705 -13 -19.3 58.2 -6.3 0 -4.8

GTCTCTCTTGTACATTGGCC 749 SEQ ID NO: 706 -13 -26.1 77.7 -13.1 0 -6.3

GGATGAGGGCTTTTTTCTGT 783 SEQ ID NO: 707 -13 -24.5 73.2 -11.5 0 -3.7

TGGCTCGGATGAGGGCTTTT 789 SEQ ID NO: 708 -13 -26.9 75.8 -12.5 -1.3 -6.1

ACATGGCTTCTAGCTTAAGT 813 SEQ ID NO: 709 -13 -22.9 68.8 -8.9 -0.9 -7.4

GGGACTTCTGTCATAGTCTG 941 SEQ ID NO: 710 -13 -24 73.2 -8.9 -2.1 -7.3

ACTCGGGTGAGCTGGTATAG 1071 SEQ ID NO: 711 -13 -25 73 -10.6 -1.3 -5.2

CTTCAAAAGTTCCAGTATCA 1154 SEQ ID NO: 712 -13 -20.4 61.9 -7.4 0 -2.5

CAGCAGGGCGGCATTGACTT 1670 SEQ ID NO: 713 -13 -27.8 76.5 -13.9 -0.8 -6.8

AGTCCAGCAGGGCGGCATTG 1674 SEQ ID NO: 714 -13 -29.6 81.3 -14.8 -1.8 -6.9

GGGTAGTTACACATTGTGTA 1693 SEQ ID NO: 715 -13 -22.3 68.4 -7.4 -1.8 -11

GATTTCGGGTAGTCGAAGAA 1742 SEQ ID NO: 716 -13 -21.5 63.1 -6.5 -2 -4.6

TTTTTTCTTCCTGTTCTTCT 1932 SEQ ID NO: 717 -13 -23.2 71.8 -10.2 0 0

AAATTCAATATCTTTAAAGC 1992 SEQ ID NO: 718 -13 -14.4 48.5 -0.8 0 -7.7

TGATTATTATGCCTTTTTAA 2010 SEQ ID NO: 719 -13 -18.3 57 -5.3 0 -3

TACCCTGATACATCATTTAT

2044 SEQ ID NO: 720 -13 -21 62.4 -8 0 -4.8 ATACCCTGATACATCATTTA

2045 SEQ ID NO: 721 -13 -21 62.4 -8 0 -5 ACACAGGTCCATTAGTACAG

2401 SEQ ID NO: 722 -13 -22.9 68.4 -9.9 0 -5.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTCCAACTACTTAGAACTGT 2851 SEQ ID NO: 723 -13 -20.4 61.6 -7.4 0 -3

TTTTTGATTTTAGTGTCTCA 3412 SEQ ID NO: 724 -13 -19.8 63.2 -6.8 0 -2.5 CAAGTCTTTCCCTGGACTCT 50 SEQ ID NO: 725 -12.9 -26.2 75.2 -11.8 -1.4 -5.1

TAGCTTCATTCCAACACTTA 683 SEQ ID NO: 726 -12.9 -21.9 65.2 -9 0 -4.6

TCTCTCTTGTACATTGGCCC 748 SEQ ID NO: 727 -12.9 -26.9 77.7 -14 0 -6..6

TTACAAAGGGACTTCTGTCA 948 SEQ ID NO: 728 -12.9 -21.1 63.6 -5.8 -2.4 -7.1

GAGGTTGTTGAGGGTGGCTC 1505 SEQ ID NO: 729 -12.9 -26.9 80.4 -13.1 -0.8 -4.2

AAGTTTTTAATTAGCGTTAC 1972 SEQ ID NO: 730 -12.9 -17.5 55.7 -4.6 0 -4.1

CAAGAACCGTTCTGTCCGTT 2177 SEQ ID NO: 731 -12.9 -25.2 69.5 -11.3 -0.9 -8.9

TGGAGCATTTGCTTTGAAAG 2645 SEQ ID NO: 732 -12.9 -20.6 61.7 -6.7 -0.9 -8.6

CAACTCTTGAGGATGTTCAA 2954 SEQ ID NO: 733 -12.9 -20.6 62.3 -6.8 -0.7 -5.2

CTTTCCCCTTTGGGGAAGAT 3028 SEQ ID NO: 734 -12.9 -26.7 73.7 -9 -4.8 -14.5

TGATTTTAGTGTCTCACGAC 3408 SEQ ID NO: 735 -12.9 -21.2 64.7 -6.8 -1.4 -5.6

TAAATGAGATTCCCGTTTTT 3427 SEQ ID NO: 736 -12.9 -20.4 60.1 -7.5 0 -2.6

GGGCTTCCGTCTCCACTTTG 372 SEQ ID NO: 737 -12.8 -29.3 81.2 -15.8 -0.4 -3.8

ACTTATTCCTTCCTCCACGC 726 SEQ ID NO: 738 -12.8 -27.6 76.3 -14.8 0 -3.3

GCAAGGCAGCATGGTTCAGA 915 SEQ ID NO: 739 -12.8 -26.2 75.3 -12.9 -0.2 -5

TACAAAGGGACTTCTGTCAT 947 SEQ ID NO: 740 -12.8 -21 63.3 -5.8 -2.4 -7.8

CCGTGAGGGGGCATTGTCAT 982 SEQ ID NO: 741 -12.8 -28.3 78 -14.6 -0.8 -6.9

ACCACTTGTCGGTAAATGTG 1411 SEQ ID NO: 742 -12.8 -22.4 64.7 -9.6 0 -4.5

ATAGTCCACTTGTTGCCCAG 1463 SEQ ID NO: 743 -12.8 -27 76.5 -14.2 0 -3

TCATGAGGTTGTTGAGGGTG 1509 SEQ ID NO: 744 -12.8 -23.7 71.6 -10.9 0 -5.9

CACTAACTCCTGTGCATGAC 1529 SEQ ID NO: 745 -12.8 -23.7 68.4 -10.9 0 -6.5 ATACGAACTCTCGTTGATCA

1572 SEQ ID NO: 746 -12.8 -21.2 62.4 -6.1 -2.3 -11.2 CATACGAACTCTCGTTGATC

1573 SEQ ID NO: 747 -12.8 -21.2 62.4 -6.1 -2.3 -8.3 CTCTTTTTGTTTTGAAAGCA

1890 SEQ ID NO: 748 -12.8 -19.8 61 -6.3 -0.5 -5.2

GAATCCTGTAAGCTCAAATC 2268 SEQ ID NO: 749 -12.8 -20.2 60.7 -7.4 0 -5

CAGTAGCAGAAATAAGGTCT 2680 SEQ ID NO: 750 -12.8 -20 61.2 -7.2 0 -3.3

CCACATTTCAGCAACAGTAG 2694 SEQ ID NO: 751 -12.8 -22.5 66 -9.7 0 -4.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CTTAGAACTGTGACTATTTG 2842 SEQ ID NO: 752 -12.8 -18.5 58.1 -5.7 0 -3.9

CTTTTGCTATTTTGTTATAT 3323 SEQ ID NO: 753 -12.8 -18.6 59.2 -5.8 0 -2.9

CATTAAGGAAATTACCGCTT 3340 SEQ- ID NO: 754 -12.8 -19.8 58 -6.3 -0.5 -3.7

TTGATTTTAGTGTCTCACGA 3409 SEQ ID NO: 755 -12.8 -21.1 64.5 -6.8 -1.4 -516

TTCCGTCTCCACTTTGGGCA 368 SEQ ID NO: 756 -12.7 -29.1 80.3 -15.4 -0.9 -5.3

CCTCCACGCATTCGGTCGGC 715 SEQ ID NO: 757 -12.7 -31.4 81.1 -17.8 -0.8 -4.8

TGGCTTCTAGCTTAAGTCCA 810 SEQ ID NO: 758 -12.7 -25.1 73.8 -10.7 -1.7 -9.7

TTTTCGTGCTTGCTTCGGTT 1237 SEQ ID NO: 759 -12.7 -26 74.6 -13.3 0 -5.7

ACTCTCGTTGATCAAACTGG 1566 SEQ ID NO: 760 -12.7 -21.5 63.5 -7.9 -0.8 -8.7

CAACCCTCAGAACATATTTA 2534 SEQ ID NO: 761 -12.7 -20.6 60.4 -7.9 . 0 -2.5

ACAAAACAACCCTCAGAACA 2540 SEQ ID NO: 762 -12.7 -20 57.6 -7.3 0 -2.5

TTCCTTTCCCCTTTGGGGAA 3031 SEQ ID NO: 763 -12.7 -28.6 77.5 -11.6 -4.3 -12.6

CGCTTTTGCTATTTTGTTAT 3325 SEQ ID NO: 764 -12.7 -21.5 64.5 -7.2 -1.5 -3.6

CCCAGCACCAATAGGTGTAA 296 SEQ ID NO: 765 -12.6 -25.7 70.7 -9.9 -3.2 -8.4

CGTCTCCACTTTGGGCAGCA 365 SEQ ID NO: 766 -12.6 -29.1 80.4 -15.9 -0.3 -6.1

AGGACAACGCTTTCTCTGTG 641 SEQ ID NO: 767 -12.6 -23.7 69 -11.1 0 -3.3

CAGTAAGGACAACGCTTTCT 646 SEQ ID NO: 768 -12.6 -22.1 64.4 -8.8 -0.4 -3.7

ACGACAGTAAGGACAACGCT 650 SEQ ID NO: 769 -12.6 -22.4 63.2 -9.1 -0.4 -4.3

ATTCGGTCGGCCCTTACAGC 706 SEQ ID NO: 770 -12.6 -29.3 79 -16.2 -0.2 -7.2

TTTTCTGTTGCTTCAGGGCC 771 SEQ ID NO: 771 -12.6 -27 79.1 -13.5 -0.7 -7.4

TCATAGTCTGTAGGAGGCAA 931 SEQ ID NO: 772 -12.6 -23 69.6 -10.4 0.2 -4

ATGTTACAAAGGGACTTCTG 951 SEQ ID NO: 773 -12.6 -20 60.9 -5.8 -1.6 -5.7

TCAAAAGTTCCAGTATCAGA 1152 SEQ ID NO: 774 -12.6 -20 61.1 -7.4 0 -2.7

TGATTTTAGCCTGGACTTGA 1191 SEQ ID NO: 775 -12.6 -22.9 67.4 -10.3 0 -4.8

TGCTCAGCTTTTCGTGCTTG 1245 SEQ ID NO: 776 -12.6 -26 75.6 -12.7 -0.4 -4.7

TAGTCCACTTGTTGCCCAGT 1462 SEQ ID NO: 777 -12.6 -28.2 80.1 -15.6 0 -3

GCCACTAACTCCTGTGCATG 1531 SEQ ID NO: 778 -12.6 -26.7 74.3 -13.5 -0.3 -6.5

CAAGGTTTTTGACATCTAAA• 1617 SEQ ID NO: 779 -12.6 -17.9 55.9 -4.6 -0.4 -3.7

GGAAGTTTTCAAGGTTTTTG 1626 SEQ ID NO: 780 -12.6 -19.8 61.6 -6.3 -0.8 -4.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol IntraInter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GTAGTCCAGCAGGGCGGCAT 1676 SEQ ID NO: 781 -12.6 -30.4 84.2 -16 -1.8 -6.9

GCTGCGGGTAGTTACACATT

1698 SEQ ID NO: 782 -12.6 -25.5 73.2 -12.9 0 -5.8 GTAACTTATGCTCTTTTGGC

1855 SEQ ID NO: 783 -12.6 -22.4 67.7 -9.8 0 -3.6

TTGTTCTACAGCAGACTTTG 3083 SEQ ID NO: 784 -12.6 -21'.7 66.5 -9.1 0 -4.1

AGAATAATTAAGTACTGTTA 3386 SEQ ID NO: 785 -12.6 -15 50.3' -2.4 0 -6.3

CTTTCACAGGTGAGGAGCCC 538 SEQ ID NO: 786 -12.5 -27.7 78.5 -14.4 -0.6 -7.1

TGTGTACCTTTTATTATTTT 587 SEQ ID NO: 787 -12.5 -19.3 60.6 -6.8 0 -4.2

GTAAGGACAACGCTTTCTCT 644 SEQ ID NO: 788 -12.5 -22.7 66.4 -10.2 0 -3.3

CATGGCTTCTAGCTTAAGTC 812 SEQ ID NO: 789 -12.5 -23.1 69.9 -8.9 -1.7 ^• -6.8

ACTCCAGCAGTTCTGAAGCA 1373 SEQ ID NO: 790 -12.5 -25.7 74.5 -12.2 -0.9 -6.5

CCTTTCCATGTACCACTTGT 1422 SEQ ID NO: 791 -12.5 -26.4 74.4 -13.9 0 -4.3

CATTGTGTAGTCCAGCAGGG 1682 SEQ ID NO: 792 -12.5 -26.1 76.5 -12.9 -0.4 -4.8

TGCTGCGGGTAGTTACACAT

1699 SEQ ID NO: 793 -12.5 -25.4 72.6 -12.9 0 -6.4 TCTCTTTTTGTTTTGAAAGC

1891 SEQ ID NO: 794 -12.5 -19.5 61.2 -6.3 -0.5 -3.8

CTTTAAAGCAAGTTTTTAAT 1981 SEQ ID NO: 795 -12.5 -15.8 51.6 -2.6 -0.4 -6.6

AGTACAGATTCGGTGACCAC 2388 SEQ ID NO: 796 -12.5 -23.8 69.1 -11.3 0 -5.3

ATTTTTTATGAAATCCAACA 2723 SEQ ID NO: 797 -12.5 -16.7 52.8 -4.2 0 -3.4

CTCATCCTTTCCTTTCTCTT 2899 SEQ ID NO: 798 -12.5 -25.7 76.1 -13.2 0 -0.5

TCTGCACAGCTACCTTTTAA 3203 SEQ ID NO: 799 -12.5 -23.5 68.5 -10.4 -0.3 -4.8

TTAGTGTCTCACGACATAGA

3403 SEQ ID NO: 800 -12.5 -21.4 65 -6.8 -2.1 -8.4 TTTAGTGTCTCACGACATAG

3404 SEQ ID NO: 801 -12.5 -20.9 64 -6.8 -1.6 -8.4 TTTTGATTTTAGTGTCTCAC

3411 SEQ ID NO: 802 -12.5 -19.9 63.5 -6.8 -0.3 -4.3

CGTTTTTGATTTTAGTGTCT 3414 SEQ ID NO: 803 -12.5 -20.7 64.1 -8.2 0 -2.3

AGTGCAGCTTGTCAAATTTC 165 SEQ ID NO: 804 -12.4 -22 66.8 -9.6 10 -5.3

AGGCGACCGCGGGCGGGGAT 340 SEQ ID NO: 805 -12.4 -33.2 81.4 -18.5 -1.9 -12.4

GGACTGTTCGCTTAAAAAAT

567 SEQ ID NO: 806 -12.4 -18.4 55.5 -5.5 -0.1 -3.5 TGGACTGTTCGCTTAAAAAA

568 SEQ ID NO: 807 -12.4 -18.4 55.5 -5.5 -0.1 -4 TTTCGTGCTTGCTTCGGTTA

1236 SEQ ID NO: 808 -12.4 -25.6 73.6 -13.2 0 -5.7

CTCGTTGATCAAACTGGAGA 1563 SEQ ID NO : 809 -12.4 -21.2 62.5 -7.9 -0.8 -8.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ATTTCGGGTAGTCGAAGAAG .1741 SEQ ID NO: 810 -12.4 -20.9 62 -6.5 -2 -4.6

TTATTATAGGGCACATCCCC 1813 SEQ ID NO: 811 -12.4 -25.5 71.7 -11.1 -2 -6.9

ATGCTCTTTTGGCATGCAAC 1848 SEQ ID NO: 812 -12.4 -24 69.7 -9.8 -1.8 -10.1

CTTTTTGTTTTGAAAGCAGA 1888 SEQ ID NO: 813 -12.4 -19.1 59.2 -6.7 0 -4.6

TTATGCCTTTTTAAATTCAA 2004 SEQ ID NO: 814 -12.4 -17.7 55.2 -5.3 0 -4.5

ACCCTGATACATCATTTATT 2043 SEQ ID NO: 815 -12.4 -21.4 63.3 -9 0 -5

CTTTGATTCACAGTTTGCAA 2070 SEQ ID NO: 816 -12.4 -21 63.5 -8.6 0 -6.8

GGGCTGTGAAGCTTTGATTC 2081 SEQ ID NO: 817 -12.4 -24.2 71.5 -8.5 -3.3 -8.2

AACAACCCTCAGAACATATT 2536 SEQ ID NO: 818 -12.4 -20.3 59.3 -7.9 0 -2.5

ACTAACAAGACTTCCTGCCA 2746 SEQ ID NO: 819 -12.4 -23.9 67.5 -11.5 . 0 -3

CCCTTTGGGGAAGATTTGAA 3023 SEQ ID NO: 820 -12.4 -23.3 65.8 -9 -1.9 -5.4

TTCCCCTTTGGGGAAGATTT 3026 SEQ ID NO: 821 -12.4 -25.9 72.2 -9 -4.5 -12.7

ATTTTAGTGTCTCACGACAT 3406 SEQ ID NO: 822 -12.4 -21.3 64.7 -6.8 -2.1 -8.4

TTATCTCCACACACGGGACA 499 SEQ ID NO: 823 -12.3 -24.9 69.7 -12.6 0 -4.2

AGTAAGGACAACGCTTTCTC 645 SEQ ID NO: 824 -12.3 -21.8 64.7 -8.8 -0.4 -3.7

GCTTAAGTCCATTGGCTCGG 801 SEQ ID NO: 825 -12.3 -26.5 74.5 -13.7 0 -7.8

CAGAGGTAGGCCTTTGGAGG 899 SEQ ID NO: 826- -12.3 -26.5 76.4 -12.6 -1.5 -8.2

TGGTTCAGAGGTAGGCCTTT 904 SEQ ID NO: 827 -12.3 -26.4 77.8 -12.6 -1.4 -8.2

ATCCTTCCTTTCCATGTACC 1428 SEQ ID NO: 828 -12.3 -27.1 76.4 -14.8 0 -4.3

TTTCAGACATACGAACTCTC 1580 SEQ ID NO: 829 -12.3 -20.2 61.3 -7.9 0 -3.5

GGTTTTTGACATCTAAACTA 1614 SEQ ID NO: 830 -12.3 -18.7 58.3 -5.3 -1 -5.6

TTTTTAATTAGCGTTACTTG 1969 SEQ ID NO: 831 -12.3 -18 56.7 -5.7 0 -4.1

GCAAGTTTTTAATTAGCGTT 1974 SEQ ID NO: 832 -12.3 -20.1 61 -7.8 0 -4.2

TTTAAATTCAATATCTTTAA 1995 SEQ ID NO: 833 -12.3 -13.2 46.3 -0.8 0 -4

TGCCTTTTTAAATTCAATAT

2001 SEQ ID NO: 834 -12.3 -17.6 54.9 -5.3 0 -4.5 ATGCCTTTTTAAATTCAATA

2002 SEQ ID NO: 835 -12.3 -17.6 54.9 -5.3 0 -4.5 TATGCCTTTTTAAATTCAAT

2003 SEQ ID NO: 836 -12.3 -17.6 54.9 -5.3 0 -4.5 GATTATTATGCCTTTTTAAA •

2009 SEQ ID NO: 837 -12.3 -17.6 55.2 -5.3 0 -4.2

TATGGAATCCTCTGGGGCTG 2095 SEQ ID NO : 838 -12 .3 -25 . 7 72 . 9 -12 . 8 -0 .3 -6 . 4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AGAGGTGCTCGGGCCTTCAA 2363 SEQ ID NO: 839 -12.3 -28.5 79 -14.7 -1.4 -8.5

GGATGATGAAAAAGACTGAT 2770 SEQ ID NO: 840 -12.3 -16.5 52 -4.2 0 -2.2

CACCTCATCCTTTCCTTTCT 2902 SEQ ID NO: 841 -12.3 -27.2 77.3 -14.9 0 -0.5

TGTTCTACAGCAGACTTTGG 3082 SEQ ID NO: 842 -12.3 -22.8 68.8 -10.5 0 -4.1

TTGTCCTCCCATATTTGTTC 3097 SEQ ID NO: 843 -12.3 -25.3 73.9 -13 0 -2.1

CCTGTGGCATCGCATGTTAA 3155 SEQ ID NO: 844 -12.3 -25.8 71.9 -12.6 -0.7 -5.3

ATACCTGTGGCATCGCATGT 3158 SEQ ID NO: 845 -12.3 -26.6 74.4 -13.4 -0.7 -5.2

TTTGATTTTAGTGTCTCACG 3410 SEQ ID NO: 846 -12.3 -20.6 63.5 -6.8 -1.4 -5.6

AAGTCTTTCCCTGGACTCTG 49 SEQ ID NO: 847 -12.2 -25.5 73.9 -11.8 -1.4 -5.1

ATTATAGGCAGTTCTTTGGC 214 SEQ ID NO: 848 -12.2 -23 70 -10.8 0 -4

CTTGTAAATCCCCAGTATCT 258 SEQ ID NO: 849 -12.2 -23.8 68.2 -11.6 0 -1.8

CGACAGTAAGGACAACGCTT 649 SEQ ID NO: 850 -12.2 -22.3 63 -10.1 0.4 -3.3

CTCTCTTGTACATTGGCCCA 747 SEQ ID NO: 851 -12.2 -27.2 77 -15 0 -6.6

CTAGCTTAAGTCCATTGGCT 804 SEQ ID NO: 852 -12.2 -24.7 72 -12 -0.1 -7.8

CATAGTCTGTAGGAGGCAAG 930 SEQ ID NO: 853 -12.2 -22.6 68.2 -9.6 -0.6 -4

CAAAAGTTCCAGTATCAGAT 1151 SEQ ID NO: 854 -12.2 -19.6 59.7 -7.4 0 -3.4

TCTCGTTGATCAAACTGGAG 1564 SEQ ID NO: 855 -12.2 -21 62.6 -7.9 -0.8 -8.2

ACATACGAACTCTCGTTGAT 1574 SEQ ID NO: 856 -12.2 -21 61.6 -6.1 -2.7 -6.7

GGCATTGACTTGTTCCTGGA 1661 SEQ ID NO: 857 -12.2 -26 74.7 -13.8 0 -6.8

ACATTGTGTAGTCCAGCAGG 1683 SEQ ID NO: 858 -12.2 -25.1 74.3 -12.9 0 -4.6

CGGGTAGTTACACATTGTGT 1694 SEQ ID NO: 859 -12.2 -23.4 69.1 -9.8 -1.2 -9.8

GGGAGGGGCTATTGTAGGTA 2336 SEQ ID NO: 860 -12.2 -26.1 76.9 -13.9 0 -3.7

TCGGGCCTTCAAAGGAAGAG 2355 SEQ ID NO: 861 -12.2 -23.8 66.8 -9.6 -2 -8.6

ACGAGACAAAACAACCCTCA 2545 SEQ ID NO: 862 -12.2 -21.4 59.9 -8.5 -0.4 -3.9

CTAACAAGACTTCCTGCCAG 2745 SEQ ID NO: 863 -12.2 -23.7 67.2 -11.5 0 -3

AACTCTTGAGGATGTTCAAT 2953 SEQ ID NO: 864 -12.2 -19.9 61 -6.8 -0.7 -5.2

TTCATACCTGTGGCATCGCA 3161 SEQ ID NO: 865 -12.2 -26.6 74.3 -13.5 -0.7 -4.3

ATACTTTATTTTAAACAAAT 3234 SEQ ID NO: 866 -12.2 -12.8 45.2 -0.3 0 -4.4

TAAGGAAATTACCGCTTTTG 3337 SEQ ID NO: 867 -12.2 -19.2 57.1 -6.3 -0.5 -3.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ACAAGCAAGTCTTTCCCTGG 55 SEQ ID NO: 868 -12.1 -25.2 71.6 -13.1 0 -4.1

AAGTGCAGCTTGTCAAATTT 166 SEQ ID NO: 869 -12.1 -20.9 63 -8.8 0 -6.2

AATTATAGGCAGTTCTTTGG 215 SEQ ID NO: 870 -12.1 -20.5 63.2 -8.4 0 -4

TTAGTGAAATTATAGGCAGT 222 SEQ ID NO: 871 -12.1 -18.6 58.4 -6.5 0 -4

AATTGAGACACTTGCATGTT 436 SEQ ID NO: 872 -12.1 -20.5 61.9 -7.9 -0.1 -6.8

CCAACACTTAGACATTTTTG 673 SEQ ID NO: 873 -12.1 -19.7 59.4 -7.6 0 -2.5

ACATTGGCCCAAACTTATTC 738 SEQ ID NO: 874 -12.1 -22.7 64.9 -10.6 0 -5.9

GGTTCAGAGGTAGGCCTTTG 903 SEQ ID NO: 875 -12.1 -26.4 77.8 -12.6 -1.7 -8.2

TTCCAGTATCAGATGTGGGA 1145 SEQ ID NO: 876 -12.1 -24 71.3 -11.3 -0.3 -5.9

TTCAAAAGTTCCAGTATCAG 1153 SEQ ID NO: 877 -12.1 -19.5 60.1 -7.4 0 -2

AATAGTCCACTTGTTGCCCA 1464 SEQ ID NO: 878 -12.1 -26.3 73.7 -14.2 0 -3

TACGAACTCTCGTTGATCAA 1571 SEQ ID NO: 879 -12.1 -20.5 60.4 -6.1 -2.3 -11.2

CTTGTTCCTGGACACCTTCT 1653 SEQ ID NO: 880 -12.1 -26.8 76.5 -14 -0.5 -6.3

TAGTTACACATTGTGTAGTC 1690 SEQ ID NO: 881 -12.1 -20.3 64.6 -6.1 -2 -11.4

TTCGGGTAGTCGAAGAAGTA 1739 SEQ ID NO: 882 -12.1 -21.7 64.2 -7.9 -1.7 -4

TTTTAAATTCAATATCTTTA 1996 SEQ ID NO: 883 -12.1 -14 48.2 -1.9 0 -4.5

TATTATGCCTTTTTAAATTC 2006 SEQ ID NO: 884 -12.1 -17.4 55.2 -5.3 0 -4.5

ATTAGTATTTGATTATTATG 2019 SEQ ID NO: 885 -12.1 -15.1 51.1 -3 0 -1.4

ACAGTAGCAGAAATAAGGTC 2681 SEQ ID NO: 886 -12.1 -19.3 59.8 -7.2 0 -4.1

TTTCCCCTTTGGGGAAGATT 3027 SEQ ID NO: 887 -12.1 -25.9 72.2 -9 -4.8 -14.5

TCATACCTGTGGCATCGCAT 3160 SEQ ID NO: 888 -12.1 -26.5 73.9 -13.5 -0.7 -4.6

TTTTAGTGTCTCACGACATA 3405 SEQ ID NO: 889 -12.1 -21 64.1 -6.8 -2.1 -8.4

GTGCTTTAAAGACTCTTGTA 272 SEQ ID NO: 890 -12 -20.4 63 -7.9 0 -8.1

GACAACGCTTTCTCTGTGTT 639 SEQ ID NO: 891 -12 -23.8 69.8 -11.1 -0.4 -4.2

CTAGCTTCATTCCAACACTT 684 SEQ ID NO: 892 -12 -23.1 67.7 -11.1 0 -4.6

GCTCGGATGAGGGCTTTTTT 787 SEQ ID NO: 893 -12 -25.9 74.2 -12.5 -1.3 -6.1

AGCTTAAGTCCATTGGCTCG 802 SEQ ID NO: 894 -12 -25.3 72.2 -12.8 -0.1 -7.8

AGCTGGTATAGGGGTCTGGG 1062 SEQ ID NO: 895 -12 -27 79.4 -15 0 -4.3

GGACTTGAGGCTCATCTGGC 1179 SEQ ID NO: 896 -12 -26.9 78.2 -14.9 0 -5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ATGATTTTAGCCTGGACTTG 1192 SEQ ID NO: 897 -12 -22.3 66 -10.3 0 -4.8

GAATAGTCCACTTGTTGCCC 1465 SEQ ID NO: 898 -12 -26.2 73.9 -14.2 0 -3

TTTTGCCACTAACTCCTGTG 1535 SEQ ID NO: 899 -12 -24.5 70.1 -12 -0.1 -4

AGTTTTGCCACTAACTCCTG 1537 SEQ ID NO: 900 -12 -24.5 70.5 -12 -0.1 -3.4

TCAGACATACGAACTCTCGT 1578 SEQ ID NO: 901 -12 -22 64.1 -7.9 -2.1 -6.6

TGCAATACAAATACCCTGAT 2055 SEQ ID NO: 902 -12 -20.4 59 -8.4 0 -4.7

GAAGAGGGAGGGGCTATTGT 2341 SEQ ID NO: 903 -12 -24.8 72.3 -12.8 0 -3.7

CTCGGGCCTTCAAAGGAAGA 2356 SEQ ID NO: 904 -12 -24.7 68.4 -10.7 -2 -8.6

AGGAAATTACCGCTTTTGCT 3335 SEQ ID NO: 905 -12 -22.9 65.1 -9.3 -1.5 -5.5

AGTGTCTCACGACATAGAAT 3401 SEQ ID NO: 906 -12 -20.9 63 -6.8 -2.1 -6.7

AGTGAAATTATAGGCAGTTC 220 SEQ ID NO: 907 -11.9 -19.3 60.4 -7.4 0 -4

ACTTTGGGCAGCATGACAAG 358 SEQ ID NO: 908 -11.9 -23.5 67.9 -10.5 -1 -5.3

CTTCCGTCTCCACTTTGGGC 369 SEQ ID NO: 909 -11.9 -29.3 81.2 -16.4 -0.9 -4.3

AAGGACAACGCTTTCTCTGT 642 SEQ ID NO: 910 -11.9 -23 66.8 -11.1 0 -3.3

ACAGTAAGGACAACGCTTTC 647 SEQ ID NO: 911 -11.9 -21.4 63.1 -8.8 -0.4 -3.7

CCCAAACTTATTCCTTCCTC 731 SEQ ID NO: 912 -11.9 -25.4 70.5 -13.5 0 -1.3

GATGAGGGCTTTTTTCTGTT 782 SEQ ID NO: 913 -11.9 -23.4 70.8 -11.5 0 -3.7

TTGGCTCGGATGAGGGCTTT 790 SEQ ID NO: 914 -11.9 -26.9 75.8 -13.6 -1.3 -6.1

GCATGGTTCAGAGGTAGGCC 907 SEQ ID NO: 915 -11.9 -27.8 80.7 -15.4 -0.1 -6.4

TCTGTAGGAGGCAAGGCAGC 925 SEQ ID NO: 916 -11.9 -26.5 77.2 -13.7 -0.7 -4.6

GACAATGGAGAAGAGAGTTT 1295 SEQ ID NO: 917 -11.9 -19.1 59 -7.2 0 -3.1

ACGAACTCTCGTTGATCAAA 1570 SEQ ID NO: 918 -11.9 -20.1 59.1 -6.1 -2 -11.4

ATTTCAGACATACGAACTCT 1581 SEQ ID NO: 919 -11.9 -19.8 59.9 -7.9 0 -3.5

TTTGGCATGCAACATTTCAA 1841 SEQ ID NO: 920 -11.9 -21.2 62.4 -8.1 -0.5 -10.1

TTTTTGTTTTGAAAGCAGAG 1887 SEQ ID NO: 921 -11.9 -18.2 57.4 -6.3 0 -4.1

GGCTGTGAAGCTTTGATTCA 2080 SEQ ID NO: 922 -11.9 -23.7 70 -8.5 -3.3 -9.7

TGTTGGTATCCATCTGTGAG 2144 SEQ ID NO: 923 -11.9 -23.6 71 -11 -0.4 -4.4

GTCCGTTTTTCTTCTGACCG 2164 SEQ ID NO: 924 -11.9 -26.3 74 -14.4 0 -3.2

TTAGGCTGTTCATGATTTGG 2445 SEQ ID NO: 925 -11.9 -22.1 67 -10.2 0 -6.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GGAGCATTTGCTTTGAAAGT 2644 SEQ ID NO: 926 -11.9 -21.8 64.9 -8.9 -0.9 -8.6

TAACAAGACTTCCTGCCAGA 2744 SEQ ID NO: 927 -11.9 -23.4 66.6 -11.5 0 -3.3

CTGTGACTATTTGACATCCT 2835 SEQ ID NO: 928 -11.9 -22.5 66.7 -10.6 0 -3

TTTCCAACTACTTAGAACTG 2852 SEQ ID NO: 929 -11.9 -19.3 58.9 -7.4 0 -2J8

TAGTGAAATTATAGGCAGTT 221 SEQ ID NO: 930 -11.8 -18.6 58.4 -6.8 0 -4

CGGAAGCCCAGCACCAATAG 302 SEQ ID NO: 931 -11.8 -26.8 70.7 -13.7 -1.2 -5.1

CAAGGCGACCGCGGGCGGGG 342 SEQ ID NO: 932 -11.8 -32.6 79 -18.5 -1.9 -12.4

TTCTGGTTTTCTATACATGT 604 SEQ ID NO: 933 -11.8 -20.9 65.3 -9.1 0 -6.3

ACTTCAAAAGTTCCAGTATC 1155 SEQ ID NO: 934 -11.8 -19.9 61.2 -7.4 -0.5 -3.9

CTCATCTGGCTCACACTTCA 1169 SEQ ID NO: 935 -11.8 -25.5 74.9 -13.7 . 0 -3.7

CCTGGACTTGAGGCTCATCT 1182 SEQ ID NO: 936 -11.8 -26.8 76.7 -15 0 -5.2

CTTTTCGTGCTTGCTTCGGT 1238 SEQ ID NO: 937 -11.8 -26.8 76.2 -15 0 -5.1

AAAGGTGCTCAGCTTTTCGT 1250 SEQ ID NO: 938 -11.8 -24.2 70.5 -11.8 -0.3 -3.5

CACTTGTTGCCCAGTAACCA 1457 SEQ ID NO: 939 -11.8 -26.8 73.8 -15 0.2 -4.3

CTTGTGATGCTATTATGGAA 1482 SEQ ID NO: 940 -11.8 -20.1 61.1 -8.3 0 -3.6

GTTCCTGGACACCTTCTACC 1650 SEQ ID NO: 941 -11.8 -27.7 77.9 -15.9 0 -6.2

TTATTATGCCTTTTTAAATT 2007 SEQ ID NO: 942 -11.8 -17.1 54.3 -5.3 0 -4.5

TGCTATTAGTATTTGATTAT 2023 SEQ ID NO: 943 -11.8 -17.7 57 -5.9 0 -3.6

CCGTTTTTCTTCTGACCGTG 2162 SEQ ID NO: 944 -11.8 -25.9 72.2 -14.1 0 -2.6

ACTCAAATTAGGCTGTTCAT 2452 SEQ ID NO: 945 -11.8 -20.9 63.3 -9.1 0 -3.7

AGTAGCAGAAATAAGGTCTA 2679 SEQ ID NO: 946 -11.8 -19 59.3 -7.2 0 -4.1

TTTTTTATGAAATCCAACAA 2722 SEQ ID NO: 947 -11.8 -16 51.1 -4.2 0 -3.4

ACTATTTGACATCCTAGCAA 2830 SEQ ID NO: 948 -11.8 -21.3 63.4 -9.5 0 -4.1

TCTCTTCCTTTCCCCTTTGG 3035 SEQ ID NO: 949 -11.8 -28.9 81 -17.1 0 -2.9

TATTTGTTCTACAGCAGACT 3086 SEQ ID NO: 950 -11.8 -21.3 65.6 -9.5 0 -4.1

ATCTGCACAGCTACCTTTTA 3204 SEQ ID NO: 951 -11.8 -24.2 70.8 -11.8 -0.3 -4.8

TGCTTTAAAGACTCTTGTAA 271 SEQ ID NO: 952 -11.7 -18.5 57.8 -6.3 0 -8.1

AAGGCGACCGCGGGCGGGGA■ 341 SEQ ID NO: 953 -11.7 -32.5 79.3 -18.5 -1.9 -12.4

GGCTTCCGTCTCCACTTTGG 371 SEQ ID NO: 954 -11.7 -29.3 81.2 -16.9 -0.5 -4.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TCGGTCGGCCCTTACAGCTT 704 SEQ ID NO: 955 -11.7 -30.2 80.9 -17.8 -0.4 -7.2

GTTCAGAGGTAGGCCTTTGG 902 SEQ ID NO: 956 -11.7 -26.4 77.8 -12.6 -2.1 -8.2

GACTCGGGTGAGCTGGTATA 1072 SEQ ID NO: 957 -11.7 -25.6 74 -12.5 -1.3 -5.6

ATAGCCCATTATGGACTCGG 1085 SEQ ID NO: 958 -11.7 -25.3 70.4 -13 -0.3 -5.1

TTCGTGCTTGCTTCGGTTAG 1235 SEQ ID NO: 959 -11.7 -25.5 73.5 -13.8 0 -5.7

GAAGAGAGTTTGATCTGCCA 1286 SEQ ID NO: 960 -11.7 -22.9 67.8 -11.2 0 -5

CAATGGAGAAGAGAGTTTGA 1293 SEQ ID NO: 961 -11.7 -18.9 58.4 -7.2 0 -2.4

AGTCCACTTGTTGCCCAGTA 1461 SEQ ID NO: 962 -11.7 ^• -28.2 80.1 -16.5 0 -3

GAAGTTTTCAAGGTTTTTGA 1625 SEQ ID NO: 963 -11.7 -19.2 60.3 -6.3 -1.1 -9

CACATTGTGTAGTCCAGCAG 1684 SEQ ID NO: 964 -11.7 -24.6 72.7 -12.9 0 -7

GTTATTATAGGGCACATCCC 1814 SEQ ID NO: 965 -11.7 -24.7 71.4 -11.4 -1.6 -6.5

ATTATTATGCCTTTTTAAAT 2008 SEQ ID NO: 966 -11.7 -17 54 -5.3 0 -4.5

GCTGTGAAGCTTTGATTCAC 2079 SEQ ID NO: 967 -11.7 -22.7 67.9 -8.5 -2.5 -9

GTACAGATTCGGTGACCACA 2387 SEQ ID NO: 968 -11.7 -24.5 69.9 -12.8 0 -6.1

AACACGAGACAAAACAACCC 2548 SEQ ID NO: 969 -11.7 -19.6 55.9 -7.9 0 -3.5

TTTTTATGAAATCCAACAAT 2721 SEQ ID NO: 970 -11.7 -15.9 50.8 -4.2 0 -3.4

ATGATGAAAAAGACTGATGT 2768 SEQ ID NO: 971 -11.7 -15.9 51 -4.2 0 -2.5

TGGATGATGAAAAAGACTGA 2771 SEQ ID NO: 972 -11.7 -16.5 52 -4.8 0 -2.2

AACCTTGAGTCAATACATCA

2920 SEQ ID NO: 973 -11.7 -20.4 61.2 -8 -0.4 -7.6 GAACCTTGAGTCAATACATC

2921 SEQ ID NO: 974 -11.7 -20.3 61.3 -7.9 -0.4 -7.4 CCTTTGGGGAAGATTTGAAT

3022 SEQ ID NO: 975 -11.7 -21.3 62.3 -9 -0.3 -3.1

TACTTTATTTTAAACAAATG 3233 SEQ ID NO: 976 -11.7 -12.8 45.2 -0.3 -0.2 -4.4

AAGGAAATTACCGCTTTTGC 3336 SEQ ID NO: 977 -11.7 -21.3 61.3 -8.7 -0.7 -4.4

GTGTCTCACGACATAGAATA 3400 SEQ ID NO: 978 -11.7 -20.6 62.2 -6.8 -2.1 -6.7

TAGTGTCTCACGACATAGAA 3402 SEQ ID NO: 979 -11.7 -20.6 62.4 -6.8 -2.1 -6.2

AGTAACCCTTAGTGAAAGTT 116 SEQ ID NO: 980 -11.6 -20.8 62.2 -8.7 -0.2 -3.8

ATAGGCAGTTCTTTGGCTTA 211 SEQ ID NO: 981 -11.6 -23.9 72.2 -11.6 -0.4 -4

TTATAGGCAGTTCTTTGGCT 213 SEQ ID NO: 982 -11.6 -23.9 72.2 -11.6 -0.4 -4.9

CCACACACGGGACAAAGCTC 493 SEQ ID NO: 983 -11.6 -25.1 68.4 -13.5 0 -5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TCCACACACGGGACAAAGCT 494 SEQ ID NO: 984 -11.6 -25.1 68.4 -13.5 0 -4.8

GCAGTTCTGGTTTTCTATAC 608 SEQ ID NO: 985 -11.6 -22.7 70.4 -11.1 0 -5.4

GAGAGCTCGTCTGGTAACTA 1116 SEQ ID NO: 986 -11.6 -23.8 70.4 -11.3 -0.3 -9.3

ACATAAGCCCAAAGGTGCTC 1260 SEQ ID NO: 987 -11.6 -24.5 68.7 -11.8 -1 -6'.2

TTCAGACATACGAACTCTCG 1579 SEQ ID NO: 988 -11.6 -20.9 61.4 -7.9 -1.3 -5.1

CCTTCTACCAGCTGGAAGTT 1639 SEQ ID NO: 989 -11.6 -26 73.9 -12.1 -1 -12.7

GGTAGTTACACATTGTGTAG 1692 SEQ ID NO: 990 -11.6 -21.1 65.8 -7.4 -2 -11.4

CCCTGATACATCATTTATTT 2042 SEQ ID NO: 991 -11.6 -21.3 63 -9.7 0 -5

AATACCCTGATACATCATTT 2046 SEQ ID NO: 992 -11.6 -20.6 60.9 -9 0 -5

TTGCAATACAAATACCCTGA 2056 SEQ ID NO: 993 -11.6 -20.5 59.3 -8.4 -0.2 -6.6

TGAAGCTTTGATTCACAGTT 2075 SEQ ID NO: 994 -11.6 -20.8 63.5 -8.5 -0.5 -7.2

ATGGAATCCTCTGGGGCTGT 2094 SEQ ID NO: 995 -11.6 -27.2 76.9 -15 -0.3 -6.4

TGATGCATTCTTGAGAATTG 2312 SEQ ID NO: 996 -11.6 -19.2 59.1 -7.1 -0.2 -7.6

CTCAAATTAGGCTGTTCATG 2451 SEQ ID NO: 997 -11.6 -20.7 62.6 -9.1 0 -4.1

GACTTCCTGCCAGAAATTTT 2738 SEQ ID NO: 998 -11.6 -23.1 66.3 -11.5 0 -5.3

GTTTCCAACTACTTAGAACT 2853 SEQ ID NO: 999 -11.6 -20.5 62 -8.9 0 -3

CAATTTTGTTTCCAACTACT 2860 SEQ ID NO: 1000 -11.6 -20 60.4 -7.7 -0.5 -4

CATAGAATAATTAAGTACTG 3389 SEQ ID NO: 1001 -11.6 -14.4 48.6 -2.8 0 -6.3

TTAAATTGAGACACTTGCAT 439 SEQ ID NO: 1002 -11.5 -18.3 56.5 -6.8 0 -5.1

ATGGTTCAGAGGTAGGCCTT 905 SEQ ID NO: 1003 -11.5 -26.3 77.4 -13.3 -1.4 -8.2

AAAAGTTCCAGTATCAGATG 1150 SEQ ID NO: 1004 -11.5 -18.9 58.4 -7.4 0 -3.6

GCACATAAGCCCAAAGGTGC 1262 SEQ ID NO: 1005 -11.5 -25.7 70.5 -12.7 -1.4 -6.3

CAGACATACGAACTCTCGTT 1577 SEQ ID NO: 1006 -11.5 -21.7 63 -7.9 -2.3 -6

TTTGAAAGCAGAGCTCCTAG 1880 SEQ ID NO: 1007 -11.5 -22.2 65.6 -9.8 -0.8 -8.4

TCTTTTTGTTTTGAAAGCAG 1889 SEQ ID NO: 1008 -11.5 -18.9 59.3 -6.7 -0.5 -5.2

CCCTCCCCACTCCCCCAATC 1909 SEQ ID NO: 1009 -11.5 -35.9 87.3 -24.4 0 -1.1

AGCAAGTTTTTAATTAGCGT 1975 SEQ ID NO: 1010 -11.5 -20 60.9 -7.8 -0.4 -4.3

TTAAATTCAATATCTTTAAA 1994 SEQ ID NO: 1011 -11.5 -12.4 44.5 -0.8 0 -4

TTTGATTCACAGTTTGCAAT 2069 SEQ ID NO: 1012 -11.5 -20.1 61.5 -8.6 0 -7.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTTCTTCTGACCGTGTTGGT 2157 SEQ ID NO: 1013 -11.5 -25.4 74.1 -12.5 -1.3 -4.6

CTGTCCGTTTTTCTTCTGAC 2166 SEQ ID NO: 1014 -11.5 -24.4 72.2 -12.9 0 -3.5

GTAAGCTCAAATCCCCCGCT 2261 SEQ ID NO: 1015 -11.5 -28.5 74.6 -16.5 -0.1 -5

AGGTGCTCGGGCCTTCAAAG 2361 SEQ ID NO: 1016 -11.5 -27.2 75.2 -14.8 -0.8 -7.8

GCAGAGGTGCTCGGGCCTTC 2365 SEQ ID NO: 1017 -11.5 -31 86.2 -17.9 -1.5 -10.3

GTTCATGATTTGGTGGAGCT 2438 SEQ ID NO: 1018 -11.5 -24.1 72.1 -12.6 0 -6.4

CACGAGACAAAACAACCCTC 2546 SEQ ID NO: 1019 -11.5 -21.4 59.9 -9.9 0 -3.5

GCAGAAATAAGGTCTAAGTT 2675 SEQ ID NO: 1020 -11.5 -18.7 58 -7.2 0 -3.4

CAGCAACAGTAGCAGAAATA 2686 SEQ ID NO: 1021 -11.5 -19.7 59.4 -7.2 -0.9 -4.5

AGACTTCCTGCCAGAAATTT 2739 SEQ ID NO: 1022 -11.5 -23 66.2 -11.5 0 -5.1

ACAAGACTTCCTGCCAGAAA

2742 SEQ ID NO: 1023 -11.5 -23 65.1 -11.5 0 -3.3 AACAAGACTTCCTGCCAGAA

2743 SEQ ID NO: 1024 -11.5 -23 65.1 -11.5 0 -3.3 TGTTTCCAACTACTTAGAAC

2854 SEQ ID NO: 1025 -11.5 -19.6 60 -7.4 -0.5 -3.4

CTTTCCTTTCTCTTTGCATA 2893 SEQ ID NO: 1026 -11.5 -23.6 70.8 -12.1 0 -5.1

ACTCTTGAGGATGTTCAATT 2952 SEQ ID NO: 1027 -11.5 -20.7 63.5 -8.3 -0.7 -5.2

TATAGGCAGTTCTTTGGCTT 212 SEQ ID NO: 1028 -11.4 -23.9 72.2 -12.5 0.4 -4

CTTAGTGAAATTATAGGCAG 223 SEQ ID NO: 1029 -11.4 -18.3 57.3 -6.9 0 -4

CCGTGTCGGTCCGGAAGCCC 313 SEQ ID NO: 1030 -11.4 -32.9 82.6 -19.8 -0.9 -11.4

GTCTCCACTTTGGGCAGCAT 364 SEQ ID NO: 1031 -11.4 -28.3 80.8 -15.9 -0.9 -6.1

TAAATTGAGACACTTGCATG 438 SEQ ID NO: 1032 -11.4 -18.2 56.1 -6.8 0 -5.1

ACAACGCTTTCTCTGTGTTT 638 SEQ ID NO: 1033 -11.4 -23.3 68.8 -11.1 -0.6 -4.3

TGCCGTGAGGGGGCATTGTC 984 SEQ ID NO: 1034 -11.4 -29.4 81.2 -15.5 -2.5 -8.1

GCTCACTCCAGCAGTTCTGA 1377 SEQ ID NO: 1035 -11.4 -27.7 80.7 -15.3 -0.9 -5.2

ACTTGTTCCTGGACACCTTC 1654 SEQ ID NO: 1036 -11.4 -26.1 75.1 -14 -0.5 -6.3

GGTGCTTGTAGTAGAGGTAT

1788 SEQ ID NO: 1037 -11.4 -23.7 73.1 -12.3 0 -3.6 AGGTGCTTGTAGTAGAGGTA

1789 SEQ ID NO: 1038 -11.4 -23.7 73.5 -12.3 0 -3.6 ACATCCCCGTTCAGGTGCTT

1801 SEQ ID NO: 1039 -11.4 -29.7 80.9 -17.8 -0.1 -4.4

GTTGTAACTTATGCTCTTTT 1858 SEQ ID NO: 1040 -11.4 -20.7 64.3 -9.3 0 -3.6

CCCCCAATCTCTTTTTGTTT 1898 SEQ ID NO: 1041 -11.4 -26.4 73.5 -15 0 -2.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TCCTGTTCTTCTTCCCCCTC 1924 SEQ ID NO: 1042 -11.4 -31.1 86.7 -19.7 0 0

TAAATTCAATATCTTTAAAG 1993 SEQ ID NO: 1043 -11.4 -12.3 44.3 -0.8 0 -7.4

GTCTTTTATATGGAATCCTC 2103 SEQ ID NO: 1044 -11.4 -21 64.4 -9.6 0 -6.4

CCATGGAGGAATCCTGTAAG 2276 SEQ ID NO: 1045 -11.4 -23.1 66 -8.9 -2.8 -7.9

CAAAGGAAGAGGGAGGGGCT 2346 SEQ ID NO: 1046 -11.4 -24.3 68.7 -12.9 0 -3.7

ATTAGGCTGTTCATGATTTG 2446 SEQ ID NO: 1047 -11.4 -20.9 64.2 -9.5 0 -6.4

AGCAGAAATAAGGTCTAAGT 2676 SEQ ID NO: 1048 -11.4 -18.6 57.9 -7.2 0 -4.1

TACTAACAAGACTTCCTGCC 2747 SEQ ID NO: 1049 -11.4 -22.9 65.9 -11.5 0 -3

TGATGAAAAAGACTGATGTA 2767 SEQ ID NO: 1050 -11.4 -15.6 50.5 -4.2 0 -2.4

CAACTACTTAGAACTGTGAC 2848 SEQ ID NO: 1051 -11.4 -18.7 57.9 -7.3 0 -3.3

CTGCACAGCTACCTTTTAAA 3202 SEQ ID NO: 1052 -11.4 -22.4 64.9 -10.4 -0.3 -4.8

GAATTCATAAAGTTACAAGC 69 SEQ ID NO: 1053 -11.3 -16.4 52.7 -5.1 0 -6.7

TTTCACAGGTGAGGAGCCCA 537 SEQ ID NO: 1054 -11.3 -27.5 77.6 -15.4 -0.6 -7.2

CTCTGTGTTTTGTCAATTTG 628 SEQ ID NO: 1055 -11.3 -20.7 64.4 -9.4 0 -3.8

TGTCTCTCTTGTACATTGGC 750 SEQ ID NO: 1056 -11.3 -24.1 73.6 -12.8 0 -6.3

TTTCTGTTGCTTCAGGGCCC 770 SEQ ID NO: 1057 -11.3 -28.9 82.3 -16.4 -0.7 -10

TCATCTGGCTCACACTTCAA 1168 SEQ ID NO: 1058 -11.3 -23.9 70.4 -12.6 0 -3.7

ACAATGGAGAAGAGAGTTTG 1294 SEQ ID NO: 1059 -11.3 -18.5 57.6 -7.2 0 -3.1

AAGATGGATCCTTCCTTTCC 1435 SEQ ID NO: 1060 -11.3 -25 71.5 -12.5 -1 -9.5

TGAGGTTGTTGAGGGTGGCT 1506 SEQ ID NO: 1061 -11.3 -26.5 78.2 -15.2 0 -3.7

CCAATCTCTTTTTGTTTTGA 1895 SEQ ID NO: 1062 -11.3 -21.1 64 -9.8 0 -2.8

AGTTTTTAATTAGCGTTACT 1971 SEQ ID NO: 1063 -11.3 -19.1 59.6 -7.8 0 -4.1

TTTTCTTCTGACCGTGTTGG 2158 SEQ ID NO: 1064 -11.3 -24.3 71 -12.5 -0.2 -3.5

GGAAGAGGGAGGGGCTATTG 2342 SEQ ID NO: 1065 -11.3 -24.8 71.5 -13.5 0 -3.7

TCAAATTAGGCTGTTCATGA 2450 SEQ ID NO: 1066 -11.3 -20.4 62 -9.1 0 -6.1

CAAAACAACCCTCAGAACAT 2539 SEQ ID NO: 1067 -11.3 -19.8 57.1 -8.5 0 -2.5

GCCACATTTCAGCAACAGTA 2695 SEQ ID NO: 1068 -11.3 -24.3 70 -13 0 -4.1

CAAGACTTCCTGCCAGAAAT 2741 SEQ ID NO: 1069 -11.3 -22.8 64.6 -11.5 0 -3.3

TGAACCTTGAGTCAATACAT 2922 SEQ ID NO: 1070 -11.3 -19.9 59.8 -7.9 -0.4 -7.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CTTTGGGGAAGATTTGAATT 3021 SEQ ID NO: 1071 -11.3 -19.4 59 -8.1 0 -3.2

ACTCTCTTCCTTTCCCCTTT 3037 SEQ ID NO: 1072 -11.3 -28.8 81.2 -17.5 0 0

GTTCTACAGCAGACTTTGGT 3081 SEQ ID NO: 1073 -11.3 -24 72.6 -12.7 0 -4.2

TTTCATACCTGTGGCATCGC 3162 SEQ ID NO: 1074 -11.3 -26 73.6 -14.7 0 -4

ATTAAAGTCTAAATGAGATT 3436 SEQ ID NO: 1075 -11.3 -14.5 48.9 -2.6 -0.3 -4.9

TCCGTCTCCACTTTGGGCAG 367 SEQ ID NO: 1076 -11.2 -29 80.2 -16.8 -0.9 -5.3

GAGACACTTGCATGTTTTCC 432 SEQ ID NO: 1077 -11.2 -23.7 70 -12 -0.1 -6.8

ATGTGTACCTTTTATTATTT 588 SEQ ID NO: 1078 -11.2 -19.2 60.3 -8 0 -4.2

ATTGGCTCGGATGAGGGCTT 791 SEQ ID NO: 1079 -11.2 -26.8 75.4 -14.7 -0.8 -5.5

CTGGAGAGCTCGTCTGGTAA 1119 SEQ ID NO: 1080 -11.2 -25.1 72.9 -13.2 -0.3 -8.7

CCACTTGTTGCCCAGTAACC 1458 SEQ ID NO: 1081 -11.2 -28.1 76.1 -16.2 -0.5 -4.3

CTATTATGGAATAGTCCACT 1473 SEQ ID NO: 1082 -11.2 -20.6 62.2 -7 -2.4 -9.7

GGGTGGCTCCGGCTTGTGAT 1494 SEQ ID NO: 1083 -11.2 -30.5 83.8 -18.1 -1.1 -6.6

TGGAAGTTTTCAAGGTTTTT 1627 SEQ ID NO: 1084 -11.2 -19.8 61.6 -7.7 -0.8 -3.8

CAGGTGCTTGTAGTAGAGGT 1790 SEQ ID NO: 1085 -11.2 -24.7 75.4 -13.5 0 -2.9

CTTCCTGTTCTTCTTCCCCC 1926 SEQ ID NO: 1086 -11.2 -30.8 85.1 -19.6 0 0

TCCGTTTTTCTTCTGACCGT 2163 SEQ ID NO: 1087 -11.2 -26.3 74 -15.1 0 -2.6

GTTTCAGTTCAGCTTTACCA 2293 SEQ ID NO: 1088 -11.2 -24.4 73.5 -13.2 0 -4.6

GGAGGGGCTATTGTAGGTAC 2335 SEQ ID NO: 1089 -11.2 -25.1 74.7 -13.9 0 -4

TTCATGATTTGGTGGAGCTA 2437 SEQ ID NO: 1090 -11.2 -22.6 68 -11.4 0 -6.4

ATGAAAAAGACTGATGTATA 2765 SEQ ID NO: 1091 -11.2 -14.7 48.8 -3.5 0 -2.4

ACTGTGACTATTTGACATCC 2836 SEQ ID NO: 1092 -11.2 -21.8 65.3 -10.6 0 -3

ATTTGTTCTACAGCAGACTT 3085 SEQ ID NO: 1093 -11.2 -21.7 66.6 -10.5 0 -4.1

GCGATTCTTTGTCCTCCCAT

3105 SEQ ID NO: 1094 -11.2 -28.4 78.2 -17.2 10 -3.4 TGCGATTCTTTGTCCTCCCA

3106 SEQ ID NO: 1095 -11.2 -28.4 78.1 -17.2 0 -4 AGACATTCTTAGTGAAATTA

230 SEQ ID NO: 1096 -11.1 -16.9 54.6 -5.8 0.1 -3.6

TTAAAGACTCTTGTAAATCC 267 SEQ ID NO: 1097 -11.1 -17.4 54.8 -6.3 0 -4.8

CTCCACACACGGGACAAAGC 495 SEQ ID NO: 1098 -11.1 -25.1 68.4 -13.5 -0.2 -4.2

ACTTTATCTCCACACACGGG 502 SEQ ID NO: 1099 -11.1 -24.6 69.6 -13.5 0 -3.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GTGTTTTGTCAATTTGGCAG 624 SEQ ID NO: 1100 -11.1 -22.2 67.5 -10.3 -0.6 -7.6

AGGGCATAGCTTGGATCACC 837 SEQ ID NO: 1101 -11.1 -26.5 75.6 -14.7 -0.5 -5.9

TTCAGAGGTAGGCCTTTGGA 901 SEQ ID NO: 1102 -11.1 -25.8 75.5 -12.6 -2.1 -8.2

ATATATGAATAGCCCATTAT 1093 SEQ ID NO: 1103 -11.1 -19.3 58.2 -8.2 0 -5

GGAGAAGAGAGTTTGATCTG 1289 SEQ ID NO: 1104 -11.1 -20.2 62.6 -9.1 0 -5

TCACTCCAGCAGTTCTGAAG 1375 SEQ ID NO: 1105 -11.1 -24.3 71.7 -12.2 -0.9 -5.2

GAGCTCACTCCAGCAGTTCT 1379 SEQ ID NO: 1106 -11.1 -27.7 81.4 -15.1 -1.4 -8.6

AGATGGATCCTTCCTTTCCA 1434 SEQ ID NO: 1107 -11.1 -26.4 75 -13.7 -1.6 -9.5

GGCTTGTGATGCTATTATGG 1484 SEQ ID NO: 1108 -11.1 -23.2 68.8 -11.4 -0.5 -4.5

GCCTGCATACTGATGGCCCG 1762 SEQ ID NO: 1109 -11.1 -30.4 79.2 -17.9 -1.3 -6.6

GCAGAGCTCCTAGGGGTTGT 1873 SEQ ID NO: 1110 -11.1 -28.9 83.9 -17.1 -0.2 -9

GCCTTTTTAAATTCAATATC 2000 SEQ ID NO: 1111 -11.1 -18 56.1 -6.9 . 0 -4.2

ACAAATACCCTGATACATCA 2049 SEQ ID NO: 1112 -11.1 -20.6 60 -9.5 0 -4.8

TGTCCGTTTTTCTTCTGACC 2165 SEQ ID NO: 1113 -11.1 -25.5 73.9 -14.4 0 -3.5

AAGAGGGAGGGGCTATTGTA 2340 SEQ ID NO: 1114 -11.1 -23.9 70.3 -12.8 0 -3.7

CACTCAAATTAGGCTGTTCA 2453 SEQ ID NO: 1115 -11.1 -21.6 64.5 -10.5 0 -3.7

TCATTTCCCTTAATATTAAT 2618 SEQ ID NO: 1116 -11.1 -18.5 57 -7.4 0 -7.3

GTAGCAGAAATAAGGTCTAA 2678 SEQ ID NO: 1117 -11.1 -18.3 57.1 -7.2 0 -4.1

ACTTCCTGCCAGAAATTTTT 2737 SEQ ID NO: 1118 -11.1 -22.6 65.3 -11.5 0 -5.3

GATGATGAAAAAGACTGATG 2769 SEQ ID NO: 1119 -11.1 -15.3 49.7 -4.2 0 -2.2

CTCTCTTCCTTTCCCCTTTG 3036 SEQ ID NO: 1120 -11.1 -28.6 80.4 -17.5 0 0

CACTCTCTTCCTTTCCCCTT 3038 SEQ ID NO: 1121 -11.1 -29.4 81.8 -18.3 0 0

TTTGTCCTCCCATATTTGTT 3098 SEQ ID NO: 1122 -11.1 -25 72.6 -13.9 0 -2.1

GCTTTAAAGACTCTTGTAAA 270 SEQ ID NO: 1123 -11 -17.8 55.9 -6.3 0 -8.1

GGCGACCGCGGGCGGGGATG 339 SEQ ID NO: 1124 -11 -33.2 81 -20.2 -1 -12

CACTTTGGGCAGCATGACAA 359 SEQ ID NO: 1125 -11 -24.2 68.8 -12.3 -0.8 -5.3

CCCCATGCGATCGAGCCAGT 396 SEQ ID NO: 1126 -11 -31.4 80 -19.7 -0.1 -8.8

TATCTCCACACACGGGACAA- 498 SEQ ID NO: 1127 -11 -24.1 67.3 -12.6 -0.2 -4.2

TCTCTGTGTTTTGTCAATTT 629 SEQ ID NO: 1128 -11 -21.1 66.1 -10.1 0 -2.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AACGACAGTAAGGACAACGC 651 SEQ ID NO: 1129 -11 -20.8 59.6 -9.1 -0.4 -4.3

ATGAGGGCTTTTTTCTGTTG 781 SEQ ID NO: 1130 -11 -22.8 69.2 -11.8 0 -3.7

TCAGAGGTAGGCCTTTGGAG 900 SEQ ID NO: 1131 -11 -25.7 75.5 -12.6 -2.1 -8.2

AGTTTGATCTGCCATTTTGC 1280 SEQ ID NO: 1132 -11 -23.9 70.9 -12.9 0 -4.2

AATGGAGAAGAGAGTTTGAT 1292 SEQ ID NO: 1133 -11 -18.2 57. ϊ -7.2 0 -1.3

TGTACCACTTGTCGGTAAAT

1414 SEQ ID NO: 1134 -11 -22.1 64.3 -9.9 -1.1 -6.5 ATGTACCACTTGTCGGTAAA

1415 SEQ ID NO: 1135 -11 -22.1 64.3 -9.9 -1.1 -6.5 GTTTTTGACATCTAAACTAA

1613 SEQ ID NO: 1136 -11 -16.8 53.9 -5.3 -0.2 -4.7

AGCTGGAAGTTTTCAAGGTT 1630 SEQ ID NO: 1137 -11 -22.2 67.1 -11.2 0 -5.9

TTCTACCAGCTGGAAGTTTT 1637 SEQ ID NO: 1138 -11 -23.3 69 -10.5 0 -11.8

ACCTTCTACCAGCTGGAAGT 1640 SEQ ID NO: 1139 -11 -26.1 74.1 -12.8 -1 -12.7

TGTAGTCCAGCAGGGCGGCA 1677 SEQ ID NO: 1140 -11 -30.4 84 -17.6 -1.8 -6.9

TCGGGTAGTCGAAGAAGTAG 1738 SEQ ID NO: 1141 -11 -21.6 64.1 -9.7 -0.7 -2

CAGCCTGCATACTGATGGCC 1764 SEQ ID NO: 1142 -11 -28.3 77.5 -15.2 -2.1 -7.4

TCCCCCAATCTCTTTTTGTT 1899 SEQ ID NO: 1143 -11 -26.7 74.7 -15.7 0 -2.6

TTTTTAAATTCAATATCTTT 1997 SEQ ID NO: 1144 -11 -14.4 49 -3.4 0 -4.5

TTGCTATTAGTATTTGATTA 2024 SEQ ID NO: 1145 -11 -17.8 57.4 -6.8 0 -3.6

CGTTTTTCTTCTGACCGTGT 2161 SEQ ID NO: 1146 -11 -25.1 71.9 -14.1 0 -3.6

TGCTCGGGCCTTCAAAGGAA 2358 SEQ ID NO: 1147 -11 -25.9 70.7 -14 -0.8 -8.6

TGACACAGGTCCATTAGTAC 2403 SEQ ID NO: 1148 -11 -22.8 68.2 -10.4 -1.3 -6.2

AACAGTAGCAGAAATAAGGT 2682 SEQ ID NO: 1149 -11 -18.2 56.5 -7.2 0 -4.1

CTTCCTGCCAGAAATTTTTT 2736 SEQ ID NO: 1150 -11 -22.5 65.1 -11.5 0 -5.3

GGTCAGTATCACTCTCTTCC 3047 SEQ ID NO: 1151 -11 -25.7 78.3 -14.7 0 -2.5

AACCCTTAGTGAAAGTTAAG 113 SEQ ID NO: 1152 -10.9 -18.9 57.4 -7.5 -0.2 -4.6

TAGGCAGTTCTTTGGCTTAA 210 SEQ ID NO: 1153 -10.9 -23.2 69.7 -11.6 -0.4 -4

ACCTTTTATTATTTTGGACT 582 SEQ ID NO: 1154 -10.9 -20.1 61.5 -9.2 0 -3.3

TTGTGATGCTATTATGGAAT 1481 SEQ ID NO: 1155 -10.9 -19.2 59.1 -8.3 0 -3.8

TTGTAGTAGAGGTATTCTTC 1783 SEQ ID NO: 1156 -10.9 -20.5 66.1 -9.1 -0.1 -2.7

GAAGCTTTGATTCACAGTTT 2074 SEQ ID NO: 1157 -10.9 -20.9 64 -10 0 -7.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ACTCCATTACAATGTCTTTT 2116 SEQ ID NO: 1158 -10.9 -21 63.5 -10.1 0 -5.1

TTCTTCTGACCGTGTTGGTA 2156 SEQ ID NO: 1159 -10.9 -25 73.1 -12.5 -1.5 -4.5

ACCATGGAGGAATCCTGTAA 2277 SEQ ID NO: 1160 -10.9 -23.3 66.4 -10.3 -2.1 -8.9

TTGAGAATTGTTTCAGTTCA 2302 SEQ ID NO: 1161 -10.9 -19.6 61.7 -7.1 -1.5 -5. '8

TCAAAGGAAGAGGGAGGGGC 2347 ^' SEQ ID NO: 1162 -10.9 -23.8 68.3 -12.9 0 -2.8

GAGGTGCTCGGGCCTTCAAA 2362 SEQ ID NO: 1163 -10.9 -27.8 76.2 -16 -0.8 -8.3

CAAATTAGGCTGTTCATGAT 2449 SEQ ID NO: 1164 -10.9 -20 60.6 -9.1 0 -6.4

ATATTAATTCACACTTACAT 2606 SEQ ID NO: 1165 -10.9 -16.7 53.7 -5.8 0 -4.2

TATTTTAAACAAATGTTGAT 3228 SEQ ID NO: 1166 -10.9 -13.7 46.9 -2.1 -0.4 -6.4

GAATAATTAAGTACTGTTAA 3385 SEQ ID NO: 1167 -10.9 -14.3 48.5 -3.4 0 -6.3

TGTAAATCCCCAGTATCTGA 256 SEQ ID NO: 1168 -10.8 -23.4 67.2 -12 -0.3 -4.1

GTGTACCTTTTATTATTTTG 586 SEQ ID NO: 1169 -10.8 -19.3 60.6 -8.5 0 -4.2

TAGCTTAAGTCCATTGGCTC 803 SEQ ID NO: 1170 -10.8 -24.2 71.7 -12.8 -0.3 -7.8

AGCTTGGATCACCTGAGACA 830 SEQ ID NO: 1171 -10.8 -24.9 71.7 -13.6 -0.2 -6.4

TAATGGGGGATGTTACAAAG 960 SEQ ID NO: 1172 -10.8 -18.9 57.4 -8.1 0 -3.1

TTGCACATAAGCCCAAAGGT 1264 SEQ ID NO: 1173 -10.8 -24 66.9 -12.7 -0.2 -5.3

AACTCTCGTTGATCAAACTG 1567 SEQ ID NO: 1174 -10.8 -19.6 59.1 -7.9 -0.8 -8.7

CTGCGGGTAGTTACACATTG 1697 SEQ ID NO: 1175 -10.8 -23.7 68.7 -12.9 0 -4.9

ATCTCTTTTTGTTTTGAAAG 1892 SEQ ID NO: 1176 -10.8 -17.7 56.9 -6.3 -0.3 -3.7

CAATCTCTTTTTGTTTTGAA 1894 SEQ ID NO: 1177 -10.8 -18.4 58.1 -7.6 0 -2.5

TTTTTTTCTTCCTGTTCTTC 1933 SEQ ID NO: 1178 -10.8 -22.4 70 -11.6 0 0

TTTAAAGCAAGTTTTTAATT 1980 SEQ ID NO: 1179 -10.8 -15 50 -3.5 -0.4 -4.8

ACAAGAACCGTTCTGTCCGT 2178 SEQ ID NO: 1180 -10.8 -25.3 69.7 -13.5 -0.9 -8.9

AATCCTGTAAGCTCAAATCC 2267 SEQ ID NO: 1181 -10.8 -21.6 63 -10.8 0 -5

TAGGCTGTTCATGATTTGGT 2444 SEQ ID NO: 1182 -10.8 -23.2 70.1 -12.4 0 -6.4

CATCTGCACAGCTACCTTTT 3205 SEQ ID NO: 1183 -10.8 -25.2 72.6 -14.4 0.4 -4.8

TCTCACGACATAGAATAATT

3397 SEQ ID NO: 1184 -10.8 -17.6 54.8 -6.8 0 -2.6 GTCTCACGACATAGAATAAT

3398 SEQ ID NO: 1185 -10.8 -18.7 57.3 -6.8 -1 -4.1 CAGTAACCCTTAGTGAAAGT

117 SEQ ID NO: 1186 -10.7 -21.4 63.1 -10 -0.4 -4.6 . kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ACAAGGCGACCGCGGGCGGG 343 SEQ ID NO: 1187 -10.7 -31.6 77.4 -18.6 -1.9 -12.4

CCTTTTATTATTTTGGACTG 581 SEQ ID NO: 1188 -10.7 -19.9 60.9 -9.2 0 -2.7

CTTCAGGGCCCTGTCTCTCT 761 SEQ ID NO: 1189 -10.7 -30.3 86.8 -15.8 -0.3 -15.8

ATAGTCTGTAGGAGGCAAGG 929 SEQ ID NO: 1190 -10.7 -23.1 69.8 -11.6 -0.6 -4

GTGAGCTGGTATAGGGGTCT 1065 SEQ ID NO: 1191 -10.7 -26.4 79.1 -14.9 -0.6 -5

TGCACATAAGCCCAAAGGTG 1263 SEQ ID NO: 1192 -10.7 -23.9 66.5 -12.7 -0.2 -5.2

TTGCCACTAACTCCTGTGCA 1533 SEQ ID NO: 1193 -10.7 -26.8 74.7 -15.2 -0.7 -5.2

CAGCTGGAAGTTTTCAAGGT 1631 SEQ ID NO: 1194 -10.7 -22.8 67.9 -11.2 -0.8 -8.3

TGACTTGTTCCTGGACACCT 1656 SEQ ID NO: 1195 -10.7 -26.2 74.2 -15 -0.2 -6.3

TCAGCCTGCATACTGATGGC 1765 SEQ ID NO: 1196 -10.7 -26.7 75.7 -14.3 -1.7 -9

TTCCTGTTCTTCTTCCCCCT 1925 SEQ ID NO: 1197 -10.7 -30.8 85.1 -20.1 0 0

GTGAAGCTTTGATTCACAGT 2076 SEQ ID NO: 1198 -10.7 -21.9 66.5 -8.5 -2.7 -8.4

TTTTTCTTCTGACCGTGTTG 2159 SEQ ID NO: 1199 -10.7 -23.2 68.8 -12.5 0 -3.2

AAGACTTCCTGCCAGAAATT 2740 SEQ ID NO: 1200 -10.7 -22.2 63.8 -11.5 0 -3.3

GTCAGTATCACTCTCTTCCT 3046 SEQ ID NO: 1201 -10.7 -25.4 77.6 -14.7 0 -2.5

CCCATATTTGTTCTACAGCA 3090 SEQ ID NO: 1202 -10.7 -24.3 70.2 -13.6 0 -4.1

TTTTGCTATTTTGTTATATC 3322 SEQ ID NO: 1203 -10.7 -18.1 58.5 -7.4 0 -3.6

AAAGTGCAGCTTGTCAAATT 167 SEQ ID NO: 1204 -10.6 -20.1 60.6 -8.8 -0.4 -7.1

CGTGCTTTAAAGACTCTTGT 273 SEQ ID NO: 1205 -10.6 -21.5 63.9 -10.4 0 -8.1

CACTTTATCTCCACACACGG 503 SEQ ID NO: 1206 -10.6 -24.1 68.2 -13.5 0 -3.5

CATGGTTCAGAGGTAGGCCT 906 SEQ ID NO: 1207 -10.6 -26.9 78.1 -15 -1.2 -8

GGCAGCOATGGTTCAGAGGTA 911 SEQ ID NO: 1208 -10.6 -26.5 78 -15.4 -0.2 -5.3

GGACTTCTGTCATAGTCTGT 940 SEQ ID NO: 1209 -10.6 -24 74.1 -11.3 -'2.1 -7.3

GTACTCAGACTTGATGGCCC 1043 SEQ ID NO: 1210 -10.6 -26.5 75.5 -15.2 -0.3 -8.3

AGGCTCATCTGGCTCACACT 1172 SEQ ID NO: 1211 -10.6 -27.3 79.2 -15.8 -0.8 -4.4

TCTTGCTGCAAATAGGCCAT 1210 SEQ ID NO: 1212 -10.6 -24.6 69.6 -13.2 0 -9.3

CCAGCAGTTCTGAAGCAGCT 1370 SEQ ID NO: 1213 -10.6 -26.9 76.9 -15.3 -0.9 -7.5

ATGGAATAGTCCACTTGTTG 1468 SEQ ID NO: 1214 -10.6 -21.6 64.7 -8.6 -2.4 -9.7

GACTTGTTCCTGGACACCTT 1655 SEQ ID NO: 1215 -10.6 -26.3 74.7 -15 -0.5 -6.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AGAGGGAGGGGCTATTGTAG 2339 SEQ ID NO: 1216 -10.6 -24.6 73.1 -14 0 -3.7

GCAACAGTAGCAGAAATAAG 2684 SEQ ID NO: 1217 -10.6 -18.3 56.3 -7.2 -0.1 -4.1

GTGTTTAATGTTGTATTTTT 2807 SEQ ID NO: 1218 -10.6 -18.2 58.8 -7.6 0 -2.5

AAATGTGTTTAATGTTGTAT 2811 SEQ ID NO: 1219 -10.6 -16.4 53.4 -5.8 0 -215

CCAGCACCAATAGGTGTAAG 295 ^' SEQ ID NO: 1220 -10.5 -23.7 67.5 -9.9 -3.3 -8.4

CACACACGGGACAAAGCTCT 492 SEQ ID NO: 1221 -10.5 -24 66.8 -13.5 0 -5

TCTGTGTTTTGTCAATTTGG 627 SEQ ID NO: 1222 -10.5 -21 65.1 -10.5 0 -4.4

ATGCTAATGGGGGATGTTAC 964 SEQ ID NO: 1223 -10.5 -22.3 65.9 -11.8 0 -3.6

ATATGTTTGGTAACCTTGCA 1007 SEQ ID NO: 1224 -10.5 -22.2 65.6 -11 -0.4 -5.5

CGACAATGGAGAAGAGAGTT 1296 SEQ ID NO: 1225 -10.5 -19.8 59.3 -9.3 . 0 -3.1

ACTTGTTGCCCAGTAACCAG 1456 SEQ ID NO: 1226 -10.5 -26.1 73 -14.9 -0.5 -3.8

TGGAATAGTCCACTTGTTGC 1467 SEQ ID NO: 1227 -10.5 -23.4 69 -10.9 -2 -8.9

TGTGATGCTATTATGGAATA 1480 SEQ ID NO: 1228 -10.5 -18.8 58.2 -8.3 0 -3.8

GAATTTCAGACATACGAACT 1583 SEQ ID NO: 1229 -10.5 -18.4 56.1 -7.9 0 -4.4

TGTAGTAGAGGTATTCTTCA 1782 SEQ ID NO: 1230 -10.5 -21.1 67.1 -10 -0.3 -3.1

GTATCCATCTGTGAGTTCAA 2139 SEQ ID NO: 1231 -10.5 -22.8 69 -12.3 0 -3.2

TGTTTCAGTTCAGCTTTACC 2294 SEQ ID NO: 1232 -10.5 -23.7 72.1 -13.2 0 -4.6

AGCTATGGAGCATTTGCTTT 2650 SEQ ID NO: 1233 -10.5 -23.8 70.5 -10.8 -2.5 -8.5

CAACAGTAGCAGAAATAAGG 2683 SEQ ID NO: 1234 -10.5 -17.7 54.9 -7.2 0 -4.1

TTTGTTCTACAGCAGACTTT 3084 SEQ ID NO: 1235 -10-.5 -21.8 67 -11.3 0 -4.1

TAAGGCAAGACTTTCATACC 3173 SEQ ID NO: 1236 -10.5 -20.9 62.2 -10.4 0 -4

ACATTAAGGAAATTACCGCT 3341 SEQ ID NO: 1237 -10.5 -19.9 58.2 -8.7 -0.5 -3.7

AATTAAAGTCTAAATGAGAT 3437 SEQ ID NO: 1238 -10.5 -13.7 47 -2.6 -0.3 -3.4

TCTTAGTGAAATTATAGGCA 224 SEQ ID NO: 1239 -10.4 -18.7 58.5 -8.3 0 -4

GACATTCTTAGTGAAATTAT 229 SEQ ID NO: 1240 -10.4 -16.9 54.4 -5.8 -0.4 -3.6

TCCGTGCTTTAAAGACTCTT 275 SEQ ID NO: 1241 -1.0.4 -22.7 66 -11.8 0 -8.1

AAATTGAGACACTTGCATGT 437 SEQ ID NO: 1242 -10.4 -19.7 59.6 -9.3 0 -6.6

TTTATCTCCACACACGGGAC• 500 SEQ ID NO: 1243 -10.4 -24.3 69 -13.4 -0.2 -4.2

GACTGTTCGCTTAAAAAATC 566 SEQ ID NO: 1244 -10.4 -17.6 54.3 -7.2 0 -3.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TAGCTTGGATCACCTGAGAC 831 SEQ ID NO: 1245 -10.4 -23.9 70 -12.5 -0.9 -6.8

TGGCCATATGTTTGGTAACC 1012 SEQ ID NO: 1246 -10.4 -24.4 69.6 -13.2 -0.5 -8.7

AGGGTGGCTCCGGCTTGTGA 1495 SEQ ID NO: 1247 -10.4 -30.5 84.2 -18.7 -1.3 -6.6

TTGGCATGCAACATTTCAAT 1840 SEQ ID NO: 1248 -10.4 -21.1 62 -9.6 -0.2 -10.1

CTCCCCCAATCTCTTTTTGT 1900 SEQ ID NO: 1249 -10.4 -27.5 76.3 -17.1 0 -2.7

TTAGTATTTGATTATTATGC 2018 SEQ ID NO: 1250 -10.4 -16.9 55.3 -6.5 0 -2.6

TTTGCTATTAGTATTTGATT 2025 SEQ ID NO: 1251 -10.4 -18.2 58.3 -7.8 0 -3.6

GAATCCTCTGGGGCTGTGAA 2091 SEQ ID NO: 1252 -10.4 -25.9 73.2 -14.9 -0.3 -4.7

AAAGGAAGAGGGAGGGGCTA 2345 SEQ ID NO: 1253 -10.4 -23.3 67 -12.9 0 -3.7

AAATTTTTTATGAAATCCAA 2725 SEQ ID NO^': 1254 -10.4 -14.4 47.9 -3.5 -0.1 -4.3

TGAGGATGTTCAATTGCAGC 2947 SEQ ID NO: 1255 -10.4 -22.5 67 -12.1 0 -6.4

TCCCATATTTGTTCTACAGC 3091 SEQ ID NO: 1256 -10.4 -24 70.6 -13.6 0 -2.9

ATAGGTGTAAGTCCGTGCTT 286 SEQ ID NO: 1257 -10.3 -24.7 72.2 -13.7 -0.4 -4.3

CATTCGGTCGGCCCTTACAG 707 SEQ ID NO: 1258 -10.3 -28.2 75.9 -17.9 0.3 -6.7

TCCACGCATTCGGTCGGCCC 713 SEQ ID NO: 1259 -10.3 -32.5 82.5 -21.3 -0.8 -7.5

GGTCTGGGTACTCAGACTTG 1050 SEQ ID NO: 1260 -10.3 -25 74.9 -10.1 -4.6 -16.3

GAGGCTCATCTGGCTCACAC 1173 SEQ ID NO: 1261 -10.3 -27 78.6 -15.8 -0.8 -4.4

AAGGTGCTCAGCTTTTCGTG 1249 SEQ ID NO: 1262 -10.3 -24.9 72.8 -14.6 0.4 -6

GACATACGAACTCTCGTTGA 1575 SEQ ID NO: 1263 -10.3 -21.6 62.8 -8.6 -2.7 -6.7

AATTTCAGACATACGAACTC 1582 SEQ ID NO: 1264 -10.3 -18.2 56.1 -7.9 0 -3.5

TGTCTGCTGCGGGTAGTTAC 1703 SEQ ID NO: 1265 -10.3 -26.3 76.9 -16 0 -7.3

CACATCCCCGTTCAGGTGCT 1802 SEQ ID NO: 1266 -10.3 -30.3 81.5 -19.5 -0.1 -4.4

AAAGCAGAGCTCCTAGGGGT 1876 SEQ ID NO: 1267 -10.3 -26.2 74.9 -15 -0.8 -8.8

AATCTCTTTTTGTTTTGAAA 1893 SEQ ID NO: 1268 -10.3 -17 54.8 -6.7 10 -2.9

GGGGCTGTGAAGCTTTGATT 2082 SEQ ID NO: 1269 -10.3 -25 72.5 -11.4 -3.3 -8.2

TTGGTATCCATCTGTGAGTT

2142 SEQ ID NO: 1270 -10.3 -23.7 71.5 -12.7 -0.4 -4.4 GTTGGTATCCATCTGTGAGT

2143 SEQ ID NO: 1271 -10.3 -24.8 74.8 -13.8 -0.4 -4.4 TCATGATTTGGTGGAGCTAC

2436 SEQ ID NO: 1272 -10.3 -22.7 68.2 -12.4 0 -5.9

GAACACGAGACAAAACAACC 2549 SEQ ID NO: 1273 -10.3 -18.2 53.8 -7.9 0 -2.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CTTAATATTAATTCACACTT 2610 SEQ ID NO: 1274 -10.3 -16.1 52.3 -5.8 0 -7.3

ATGAACCTTGAGTCAATACA 2923 SEQ ID NO: 1275 -10.3 -19.9 59.8 -8.9 -0.4 -7.6

AAGGCAAGACTTTCATACCT 3172 SEQ ID NO: 1276 -10.3 -22.1 64.7 -11.8 0 -4

GGAAATTACCGCTTTTGCTA 3334 SEQ ID NO: 1277 -10.3 -22.6 64.3 -10.7 -1.5 -5:5

CAAGCAAGTCTTTCCCTGGA 54 SEQ ID NO: 1278 -10.2 -25.6 72.3 -15.4 0 -4.8

GTGCAGCTTGTCAAATTTCG 164 SEQ ID NO: 1279 -10.2 -22.8 66.7 -12.6 0 -5.3

CCACTTTGGGCAGCATGACA 360 SEQ ID NO: 1280 -10.2 -26.9 74.6 -16.1 -0.3 -6.1

TCCCCATGCGATCGAGCCAG 397 SEQ ID NO: 1281 -10.2 -30.6 78.5 -19.7 -0.1 -8.8

GACATGGCTTCTAGCTTAAG 814 SEQ ID NO: 1282 -10.2 -22.3 66.8 -10.4 -1.7 -7.4

ATAGCTTGGATCACCTGAGA 832 SEQ ID NO: 1283 -10.2 -23.7 69.4 -12.5 . -0.9 -6.8

CTGCCGTGAGGGGGCATTGT 985 SEQ ID NO: 1284 -10.2 -29.9 81.3 -17.1 -2.6 -8.2

CATCTGGCTCACACTTCAAA 1167 SEQ ID NO: 1285 -10.2 -22.8 66.5 -12.6 0 -3.7

GCTGCAAATAGGCCATGATT 1206 SEQ ID NO: 1286 -10.2 -23.9 67.5 -13.2 0 -7.7

CTTGCTGCAAATAGGCCATG 1209 SEQ ID NO: 1287 -10.2 -24.2 68 -13.2 0 -9.3

AGAGCTCACTCCAGCAGTTC 1380 SEQ ID NO: 1288 -10.2 -26.8 79.6 -15.1 -1.4 -9.3

AAGTTTTCAAGGTTTTTGAC 1624 SEQ ID NO: 1289 -10.2 -18.8 59.5 -7.2 -1.3 -5.7

TACCAGCTGGAAGTTTTCAA 1634 SEQ ID NO: 1290 -10.2 -22.3 65.6 -9.8 -0.8 -12.7

TTACACATTGTGTAGTCCAG 1687 SEQ ID NO: 1291 -10.2 -22.1 67.1 -9.8 -2 -11.4

GTAGTCGAAGAAGTAGCTGT 1734 SEQ ID NO: 1292 -10.2 -21.9 66.4 -10.9 -0.6 -5.8

CTTTTTAAATTCAATATCTT 1998 SEQ ID NO: 1293 -10.2 -15.2 50.6 -5 0 -4.5

CCTCTGGGGCTGTGAAGCTT

2087 SEQ ID NO: 1294 -10.2 -28.4 79.7 -14.9 -3.3 -9.4 TCCTCTGGGGCTGTGAAGCT

2088 SEQ ID NO: 1295 -10.2 -28.7 81.2 -14.9 -3.6 -10.7 ATTTCTTCATAGTGGAGATC

2209 SEQ ID NO: 1296 -10.2 -20.4 64.4 -9.3 -0.8 -4.6

ATCCTGTAAGCTCAAATCCC 2266 SEQ ID NO: 1297 -10.2 -24.3 68.7 -14.1 0 -5

AATATTAATTCACACTTACA 2607 SEQ ID NO: 1298 -10.2 -16 52 -5.8 0 -4.2

TGTCTCACGACATAGAATAA 3399 SEQ ID NO: 1299 -10.2 -18.7 57.2 -6.8 -1.7 -4.9

CCGTTTTTGATTTTAGTGTC 3415 SEQ ID NO: 1300 -10.2 -21.8 66 -11.6 0 -2.6

GTAAATCCCCAGTATCTGAA 255 SEQ ID NO: 1301 -10.1 -22.7 65.2 -12 -0.3 -4.1

AGGGCTTCCGTCTCCACTTT 373 SEQ ID NO: 1302 -10.1 -29.3 81.8 -17.9 -1.2 -4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTCTCTGTGTTTTGTCAATT

630 SEQ ID NO: 1303 -10.1 -21.1 66.1 -11 0 -2.9

GACAGTAAGGACAACGCTTT

648 SEQ ID NO: 1304 -10.1 -21.6 63 -10.8 -0.4 -3.7

GGTCGGCCCTTACAGCTTCT 702 SEQ ID NO: 1305 -10.1 -30.3 83.4 -20.2 0.3 -6.6

CTAATGGGGGATGTTACAAA 961 SEQ ID NO: 1306 -10.1 -19.8 59.1 -9.7 0 -3.1

TGCTGCAAATAGGCCATGAT

1207 SEQ ID NO: 1307 -10.1 -23.8 67' -13.2 0 -7.7 AAGAGAGTTTGATCTGCCAT

1285 SEQ ID NO: 1308 -10.1 -22.3 66.4 -12.2 0 -4.9

TCCAGCAGTTCTGAAGCAGC 1371 SEQ ID NO: 1309 -10.1 -26.4 76.7 -15.3 -0.9 -6.5

GAAGATGGATCCTTCCTTTC 1436 SEQ ID NO: 1310 -10.1 -23.6 69.1 -11.9 -1.6 -9.5

CCAGGAAGATGGATCCTTCC 1440 SEQ ID NO: 1311 -10.1 -26 72.4 -13.2 -2.7 -10.9

CCACTAACTCCTGTGCATGA 1530 SEQ ID NO: 1312 -10.1 -25.5 71.4 -14.8 -0.3 -6.5

CAAGAATTTCAGACATACGA 1586 SEQ ID NO: 1313 -10.1 -18 55.2 -7.9 0 -5.1

GCGGGTAGTTACACATTGTG 1695 SEQ ID NO: 1314 -10.1 -24 70.1 -13.2 -0.4 -8.2

TATTATAGGGCACATCCCCG 1812 SEQ ID NO: 1315 -10.1 -26.2 71.4 -14.1 -2 -6.9

AAATACCCTGATACATCATT 2047 SEQ ID NO: 1316 -10.1 -19.8 58.7 -9.7 0 -5

TACAAATACCCTGATACATC 2050 SEQ ID NO: 1317 -10.1 -19.6 58.4 -9.5 0 -2.7

TTGATTCACAGTTTGCAATA 2068 SEQ ID NO: 1318 -10.1 -19.7 60.6 -9.6 0 -7.1

CGTGTTGGTATCCATCTGTG 2146 SEQ ID NO: 1319 -10.1 -25 72.8 -14.4 -0.1 -4.1

TCCTAAATTTCTTCATAGTG 2215 SEQ ID NO: 1320 -10.1 -19.2 59.8 -9.1 0 -4.9

AGGTCTAAGTTGCTTTAGCT 2666 SEQ ID NO: 1321 -10.1 -23.3 71.3 -11.8 -1.3 -6.5

AGCAACAGTAGCAGAAATAA 2685 SEQ ID NO: 1322 -10.1 -18.3 56.3 -7.2 -0.9 -4.5

CTCACGACATAGAATAATTA 3396 SEQ ID NO: 1323 -10.1 -16.9 53.1 -6.8 0 -4.1

AAGACATTCTTAGTGAAATT 231 SEQ ID NO: 1324 -10 -16.5 53.3 -5.8 -0.4 -4.1

CAATAGGTGTAAGTCCGTGC 288 SEQ ID NO: 1325 -10 -23.7 68.7 -13.7 0.4 -3.5

TTCACAGGTGAGGAGCCCAT 536 SEQ ID NO: 1326 -10 -27.4 77.1 -16.6 -0.6 -7.2

CATGTGTACCTTTTATTATT 589 SEQ ID NO: 1327 -10 -19.8 61.2 -9.8 0 -3.5

TGGCTCACACTTCAAAAGTT 1163 SEQ ID NO: 1328 -10 -21.4 63.6 -10.5 -0.7 -5

TTGCTGCAAATAGGCCATGA

1208 SEQ ID NO: 1329 -10 -23.9 67.4 -13.2 0 -9 GCTTCGGTTAGCCTGCTCTT

1226 SEQ ID NO: 1330 -10 -29 82.3 -18.5 -0.1 -5.3

AATTTCTCTGTCTGCTGCGG 1711 SEQ ID NO: 1331 -10 -25.1 72.7 -15.1 0 -6.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AAATTTCTCTGTCTGCTGCG 1712 SEQ ID NO: 1332 -10 -23.2 67.8 -13.2 0 -6.4

TTTACCATGGAGGAATCCTG 2280 SEQ ID NO: 1333 -10 -23 66.1 -10.2 -2.8 -8.9

TTTCAGTTCAGCTTTACCAT 2292 SEQ ID NO: 1334 -10 -23.2 69.8 -13.2 0 -3.8

ACACGAGACAAAACAACCCT 2547 SEQ ID NO: 1335 -10 -21.2 59.2 -11.2 0 -3 '.5

CTATTTGACATCCTAGCAAA 2829 SEQ ID NO: 1336 -10 -20.4 60.8 -9.7 -0.5 -4.2

TTAGAACTGTGACTATTTGA 2841 SEQ ID NO: 1337 -10 -18.2 57.4 -8.2 0 -3.9

ATTCTTTGTCCTCCCATATT 3102 SEQ ID NO: 1338 -10 -25 72.5 -15 0 -2.1

AGGCAGTTCTTTGGCTTAAA 209 SEQ ID NO: 1339 -9.9 -22.8 67.9 -12.2 -0.4 -4

AAAGACTCTTGTAAATCCCC 265 SEQ ID NO: 1340 -9.9 -21.6 62.3 -11.7 0 -4.8

GTCCGTGCTTTAAAGACTCT 276 SEQ ID NO: 1341 -9.9 -23.8 68.9 -13.4 0 -8.1

GGAAGCCCAGCACCAATAGG 301 SEQ ID NO: 1342 -9.9 -27.2 73 -16.4 -0.7 -4.9

CTTCATTCCAACACTTAGAC 680 SEQ ID NO: 1343 -9.9 -21.2 63.5 -11.3 0 -2.5

CAAGGCAGCATGGTTCAGAG 914 SEQ ID NO: 1344 -9.9 -24.4 71.2 -14.5 0.5 -5.3

CGTGAGGGGGCATTGTCATG 981 SEQ ID NO: 1345 -9.9 -26.3 74.3 -16.4 0 -4.4

AGAGCTCGTCTGGTAACTAT 1115 SEQ ID NO: 1346 -9.9 -23.2 69 -12.5 0 -9.3

TGAGGCTCATCTGGCTCACA 1174 SEQ ID NO: 1347 -9.9 -26.8 77.7 -15.8 -1 -4.9

CGAACTCTCGTTGATCAAAC 1569 SEQ ID NO: 1348 -9.9 -20.1 59.1 -8.6 -0.7 -11.1

AAGAATTTCAGACATACGAA 1585 SEQ ID NO: 1349 -9.9 -16.6 52.3 -6.7 0 -5.1

GGTAGTCGAAGAAGTAGCTG 1735 SEQ ID NO: 1350 -9.9 -21.9 65.7 -12 5.6 -5.3

TCTTCTGACCGTGTTGGTAT 2155 SEQ ID NO: 1351 -9.9 -24.9 72.7 -13.4 -1.5 -4.5

GTTCAGCTTTACCATGGAGG 2287 SEQ ID NO: 1352 -9.9 -24.9 72.8 -14.3 -0.2 -8.8

TAGCAGAAATAAGGTCTAAG 2677 SEQ ID NO: 1353 -9.9 -17.1 54.4 -7.2 0 -4.1

TTTTATGAAATCCAACAATG 2720 SEQ ID NO: 1354 -9.9 -15.8 50.5 -5.9 0 -2.9

TGTTTAATGTTGTATTTTTA 2806 SEQ ID NO: 13.55 -9.9 -16.7 55 -6.8 0 -2.5

ATATTTGTTCTACAGCAGAC 3087 SEQ ID NO: 1356 -9.9 -20.4 63.5 -10.5 0 -4.1

CATACCTGTGGCATCGCATG 3159 SEQ ID NO: 1357 -9.9 -26.1 72.2 -15.3 -0.7 -4.6

CTTTATTTTAAACAAATGTT 3231 SEQ .ID NO: 1358 -9.9 -14.2 48.1 -3.8 -0.2 -6.1

AAATTAAAGTCTAAATGAGA 3438 SEQ ID NO: 1359 -9.9 -13 45.5 -2.6 -0.1 -3.4

ACCCTTAGTGAAAGTTAAGA 112 SEQ ID NO: 1360 -9.8 -20.2 60.5 -9.9 -0.2 -4.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AAAAGTGCAGCTTGTCAAAT 168 SEQ ID NO: 1361 -9.8 -19.3 58.3 -8.8 -0.4 -7.1

ATCTCCACACACGGGACAAA 497 SEQ ID NO: 1362 -9.8 -23.7 65.7 -13.4 -0.2 -4.2

CGGTCGGCCCTTACAGCTTC 703 SEQ ID NO: 1363 -9.8 -30.2 80.9 -19.7 -0.4 -7.2

TACATTGGCCCAAACTTATT 739 SEQ ID NO: 1364 -9.8 -22 63 -12.2 0 -6.6

CAAAGGGACTTCTGTCATAG 945 SEQ ID NO: 1365 -9.8 -20.8 62.9 -8.9 -2.1 -5.7

TTCATTTGGTCATCAACCTT 1351 SEQ ID NO: 1366 -9.8 -22.5 66.9 -11 -1.7 -4.3

GGAATAGTCCACTTGTTGCC 1466 SEQ ID NO: 1367 -9.8 -25.4 72.9 -14.2 -1.3 -7.6

AGCCTGCATACTGATGGCCC 1763 SEQ ID NO: 1368 -9.8 -29.6 79.9 -17.7 -2.1 -7.4

AATCCTCTGGGGCTGTGAAG 2090 SEQ ID NO: 1369 -9.8 -25.3 72.2 -14.9 -0.3 -5.5

TTTCTTCATAGTGGAGATCA 2208 SEQ ID NO: 1370 -9.8 -21.1 65.8 -10.4 -0.8 -5.5

CTGATGCATTCTTGAGAATT 2313 SEQ ID NO: 1371 -9.8 -20.1 61.2 -9.8 -0.2 -7.6

AATAGAATTTCCTATTAGCT 2495 SEQ ID NO: 1372 -9.8 -18.6 57.8 -8.1 -0.5 -7.1

GAGCATTTGCTTTGAAAGTT 2643 SEQ ID NO: 1373 -9.8 -20.7 62.7 -9.9 -0.9 -8.6

GGTCTAAGTTGCTTTAGCTA 2665 SEQ ID NO: 1374 -9.8 -23 70.3 -11.8 -1.3 -6.5

TTCCTGCCAGAAATTTTTTA 2735 SEQ ID NO: 1375 -9.8 -21.3 62.7 -11.5 0 -5.3

GTTTAATGTTGTATTTTTAA 2805 SEQ ID NO: 1376 -9.8 -16 53.1 -6.2 0 -3.3

TGCACAGCTACCTTTTAAAA 3201 SEQ ID NO: 1377 -9.8 -20.8 61 -10.4 -0.3 -6.3

GACTACAGTAACCCTTAGTG 122 SEQ ID NO: 1378 -9.7 -22.6 66.5 -12.1 -0.6 -5

TTGGGAAGGACACATCAGAC 139 SEQ ID NO: 1379 -9.7 -21.9 64.7 -11.5 -0.4 -2.9

CTTTAAAGACTCTTGTAAAT 269 SEQ ID NO: 1380 -9.7 -16 52 -6.3 0 -7

CTGGTTTTCTATACATGTGT 602 SEQ ID NO: 1381 -9.7 -21.6 66.6 -11.9 0 -7.1

GGCCCACTCGACAATGGAGA 1304 SEQ ID NO: 1382 -9.7 -27.2 73 -16.7 -0.6 -6.5

CATGAGGTTGTTGAGGGTGG 1508 SEQ ID NO: 1383 -9.7 -24.5 72.6 -14.8 0 -3.7

CTTCTACCAGCTGGAAGTTT 1638 SEQ ID NO: 1384 -9.7 -24.1 70.6 -12.1 -0.5 -12.7

GAAAGCAGAGCTCCTAGGGG 1877 SEQ ID NO: 1385 -9.7 -25.6 72.8 -15 -0.8 -8.8

ATACAAATACCCTGATACAT 2051 SEQ ID NO: 1386 -9.7 -19.2 57.1 -9.5 0 -2.1

CTGTGAAGCTTTGATTCACA 2078 SEQ ID NO: 1387 -9.7 -21.6 64.8 -8.5 -3.4 -9.7

CACTCCATTACAATGTCTTT 2117 SEQ ID NO: 1388 -9.7 -21.6 64.4 -11.9 0 -4.6

GTTTTTCTTCTGACCGTGTT 2160 SEQ ID NO: 1389 -9.7 -24.4 72.4 -14.7 0 -3.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AATTAGGCTGTTCATGATTT 2447 SEQ ID NO: 1390 -9.7 -20.2 62.1 -10.5 0 -6.4

CATATTTAAATGGCAAGCTA 2522 SEQ ID NO: 1391 -9.7 -18.3 56.1 -8.6 0 -6.4

AACCCTCAGAACATATTTAA 2533 SEQ ID NO: 1392 -9.7 -19.2 57.4 -9.5 0 -2.5

TTTCCCTTAATATTAATTCA 2615 SEQ ID NO: 1393 -9.7 -18.6 57.3 -8.9 0 -7.3

TCCTGCCAGAAATTTTTTAT 2734 SEQ ID NO: 1394 -9.7 -21.2 62.4 -11.5 0 -5.3

TTGGATGATGAAAAAGACTG 2772 SEQ ID NO: 1395 -9.7 -16 51.1 -6.3 0 -2.2

CTTTGTCCTCCCATATTTGT 3099 SEQ ID NO: 1396 -9.7 -25.8 74.2 -16.1 0 -2.1

ACTTTCATACCTGTGGCATC 3164 SEQ ID NO: 1397 -9.7 -24.5 71.9 -14.8 0 -4

TTGATCCACATCTGCACAGC 3213 SEQ ID NO: 1398 -9.7 -25.2 72.4 -14.8 -0.5 -5.3

AATACTTTATTTTAAACAAA 3235 SEQ ID NO: 1399 -9.7 -12.1 43.7 -2.4 0 -4.4

TCTTTCCCTGGACTCTGTAC 46 SEQ ID NO: 1400 -9.6 -26.1 76.2 -16.5 0 -4.4

AAAAATCCCTTGCAGCTTTC 553 SEQ ID NO: 1401 -9.6 -22.4 64.1 -12.8 0 -5.2

TCTCTTGTACATTGGCCCAA 746 SEQ ID NO: 1402 -9.6 -25.6 72.6 -16 0 -6.6

CATTGGCTCGGATGAGGGCT 792 SEQ ID NO: 1403 -9.6 -27.4 76.1 -16.4 -1.3 -6.1

CTGGGTACTCAGACTTGATG 1047 SEQ ID NO: 1404 -9.6 -22.8 68.1 -12.3 -0.7 -9.2

AGCCCATTATGGACTCGGGT

1083 SEQ ID NO: 1405 -9.6 -28 76.6 -17.4 -0.9 -6.8 TAGCCCATTATGGACTCGGG

1084 SEQ ID NO: 1406 -9.6 -26.5 72.8 -16 -0.8 -5.7 CAGGAAGATGGATCCTTCCT

1439 SEQ ID NO: 1407 -9.6 -24.9 70.8 -11.8 -3.5 -12.4

GGTGGCTCCGGCTTGTGATG 1493 SEQ ID NO: 1408 -9.6 -29.3 80.9 -18.3 -1.3 -6.3

AGAATTTCAGACATACGAAC 1584 SEQ ID NO: 1409 -9.6 -17.5 54.5 -7.9 0 -5.1

TTTTTGACATCTAAACTAAA 1612 SEQ ID NO: 1410 -9.6 -14.9 49.5 -5.3 0 -2.3

TTCCTGGACACCTTCTACCA 1649 SEQ ID NO: 1411 -9.6 -27.2 75.6 -17.1 -0.1 -6.2

AGCTGTCCAAATTTCTCTGT 1720 SEQ ID NO: 1412 -9.6 -23.6 70 -14 0 -4.5

GCTCCTAGGGGTTGTAACTT 1868 SEQ ID NO: 1413 -9.6 -26 75.7 -15.7 -0.2 -8.6

AAGCAGAGCTCCTAGGGGTT 1875 SEQ ID NO: 1414 -9.6 -27 77.8 -16.5 -0.8 -8.8

CTTTTTTTCTTCCTGTTCTT

1934 SEQ ID NO: 1415 -9.6 -22.9 70.4 -13.3 0 0 ACTTTTTTTCTTCCTGTTCT

1935 SEQ ID NO: 1416 -9.6 -23 70.7 -13.4 0 -2.1 AAGCAAGTTTTTAATTAGCG

1976 SEQ ID NO: 1417 -9.6 -18.1 56 -7.8 -0.4 -4.3

TATTTGCTATTAGTATTTGA 2027 SEQ ID NO: 1418 -9.6 -17.8 57.4 -8.2 0 -3.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TGATACATCATTTATTTGCT

2039 SEQ ID NO: 1419 -9.6 -19.1 59.5 -9.5 0 -4.8 CTGATACATCATTTATTTGC

2040 SEQ ID NO: 1420 -9.6 -19.1 59.5 -9.5 0 -5 GAGGGGCTATTGTAGGTACA

2334 SEQ ID NO: 1421 -9.6 -24.6 73.1 -15 0 -5.2

TAATAGAATTTCCTATTAGC 2496 SEQ ID NO: 1422 -9.6 -17.4 55.3 -6.6 -1.1 -6.8

TTTAATGTTGTATTTTTAAA 2804 SEQ ID NO: 1423 -9.6 -14.1 48.4' -4.5 0 -4.3

TTACTTTAATATCTTTCCAG 3003 SEQ ID NO: 1424 -9.6 -18.4 58.1 -8.8 0 -2.6

CTGTGGCATCGCATGTTAAT 3154 SEQ ID NO: 1425 -9.6 -23.8 68.3 -13.5 -0.4 -5.3

TGATCCACATCTGCACAGCT 3212 SEQ ID NO: 1426 -9.6 -26 74 -15.7 -0.5 -4.9

ACATAGAATAATTAAGTACT 3390 SEQ ID NO: 1427 -9.6 -14.6 49.1 -5 0 • -6

GTAAACCATGTATCCAGTTT 2 SEQ ID NO: 1428 -9.5 -21.8 64.5 -11.8 -0.1 -4.3

TTGTAAATCCCCAGTATCTG 257 SEQ ID NO: 1429 -9.5 -22.9 66.2 -13.4 0 -3.5

AATAGGTGTAAGTCCGTGCT 287 SEQ ID NO: 1430 -9.5 -23.9 69.4 -13.7 -0.4 -4.3

CCAATAGGTGTAAGTCCGTG 289 SEQ ID NO: 1431 -9.5 -23.9 68.1 -13.7 -0.4 -4.3

CGGATGAGGGCTTTTTTCTG 784 SEQ ID NO: 1432 -9.5 -24.1 69.7 -14.6 0 -3.7

GGCATTGTCATGCTAATGGG 973 SEQ ID NO: 1433 -9.5 -24.2 70.1 -11.6 -3.1 -8.9

GTGGCCATATGTTTGGTAAC 1013 SEQ ID NO: 1434 -9.5 -23.6 69.2 -13.2 -0.5 -9

AAAGTGGCCATATGTTTGGT 1016 SEQ ID NO: 1435 -9.5 -23 67.2 -12.6 -0.5 -9

AATAGCCCATTATGGACTCG 1086 SEQ ID NO: 1436 -9.5 -23.4 65.8 -13 -0.8 -5.6

CATATATGAATAGCCCATTA 1094 SEQ ID NO: 1437 -9.5 -20 59.4 -10.5 0 -6.7

GCTCATCTGGCTCACACTTC 1170 SEQ ID NO: 1438 -9.5 -26.6 78.4 -17.1 0 -3.7

TGCTTCGGTTAGCCTGCTCT 1227 SEQ ID NO: 1439 -9.5 -28.9 81.6 -18.5 -0.7 -5.3

TGATCTGCCATTTTGCACAT

1276 SEQ ID NO: 1440 -9.5 -24.1 69.4 -13.9 -0.4 -5.9 TTGATCTGCCATTTTGCACA

1277 SEQ ID NO: 1441 -9.5 -24.2 69.7 -13.9 -0.6 -5.9 CTCCAGCAGTTCTGAAGCAG

1372 SEQ ID NO: 1442 -9.5 -25.5 74.2 -15 -0.9 -5.7

GTCCACTTGTTGCCCAGTAA 1460 SEQ ID NO: 1443 -9.5 -27.5 77.1 -18 0 -3

TGCCACTAACTCCTGTGCAT 1532 SEQ ID NO: 1444 -9.5 -26.7 74.3 -16.3 -0.7 -5.4

AAGTTTTGCCACTAACTCCT 1538 SEQ ID NO: 1445 -9.5 -23.8 68.4 -13.6 -0.5 -3.7

GATCAAACTGGAGAGAACGA 1557 SEQ ID NO: 1446 -9.5 -19.3 57.5 -9.8 0 -4.7

TTTTGACATCTAAACTAAAG 1611 SEQ ID NO: 1447 -9.5 -14.8 49.3 -5.3 0 -2.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTTTAATTAGCGTTACTTGG 1968 SEQ ID NO: 1448 -9.5 -19.1 58.9 -9.6 0 -4.1

ATCCACTCCATTACAATGTC 2120 SEQ ID NO: 1449 -9.5 -22.9 66.9 -13.4 0 -5.1

TATTAATTCACACTTACATA 2605 SEQ ID NO: 1450 -9.5 -16.4 53.2 -6.9 0 -4.2

GTCATTTCCCTTAATATTAA 2619 SEQ ID NO: 1451 -9.5 -19.7 59.9 -10.2 0 -7

TCAATTTTGTTTCCAACTAC 2861 SEQ ID NO: 1452 -9.5 -19.5 59.8 -9.3 -0.5 -4

CTGTACTTTTTCCAACATTA 32 SEQ ID NO: 1453 -9.4 -20.4 61.9 -11 0 -4.8

ATCATTGAGCAAAAGAAAAG 183 SEQ ID NO: 1454 -9.4 -14.7 48.4 -5.3 0 -4.5

TAGGTGTAAGTCCGTGCTTT 285 SEQ ID NO: 1455 -9.4 -24.8 72.6 -14.7 -0.4 -4.3

GCTTCCGTCTCCACTTTGGG 370 SEQ ID NO: 1456 -9.4 -29.3 81.2 -18.9 -0.9 -4.4

TCTGGTTTTCTATACATGTG 603 SEQ ID NO: 1457 -9.4 -20.8 64.8 -11.4 0 -6.9

CTTTCTCTGTGTTTTGTCAA 632 SEQ ID NO: 1458 -9.4 -22 68.3 -12.6 0 -2.7

TGAGACATGGCTTCTAGCTT

817 SEQ ID NO: 1459 -9.4 -23.9 71.1 -12.8 -1.7 -6.7 TCACCTGAGACATGGCTTCT

822 SEQ ID NO: 1460 -9.4 -25.6 73.7 -16.2 0 -5.2

GCCATATGTTTGGTAACCTT 1010 SEQ ID NO: 1461 -9.4 -24.2 69.4 -14.1 -0.5 -5.8

AGCTCACTCCAGCAGTTCTG 1378 SEQ ID NO: 1462 -9.4 -27.1 79.7 -16.2 -1.4 -5.3

TCTACCAGCTGGAAGTTTTC 1636 SEQ ID NO: 1463 -9.4 -23.6 70.3 -11.9 0 -12.7

ATTATAGGGCACATCCCCGT 1811 SEQ ID NO: 1464 -9.4 -27.7 75.1 -16.3 -2 -6.9

TTGAAAGCAGAGCTCCTAGG 1879 SEQ ID NO: 1465 -9.4 -23.3 67.9 -13.2 -0.3 -8.6

TGGAATCCTCTGGGGCTGTG 2093 SEQ ID NO: 1466 -9.4 -27.2 76.8 -17.2 -0.3 -6.4

CAGTTCAGCTTTACCATGGA 2289 SEQ ID NO: 1467 -9.4 -24.4 71.3 -14.3 0 -8.8

AGGCTGTTCATGATTTGGTG 2443 SEQ ID NO: 1468 -9.4 -23.5 70.5 -14.1 0 -6.4

CCCTTAATATTAATTCACAC 2612 SEQ ID NO: 1469 -9.4 -19.1 57.6 -9.7 0 -7.3

ATACTAACAAGACTTCCTGC 2748 SEQ ID NO: 1470 -9.4 -20.9 62.2 -11.5 0 -2.8

TGTAAACACTATATCTTATT 3270 SEQ ID NO: 1471 -9.4 -16.1 52.7 -6.7 0 -3.4

TGTAAACCATGTATCCAGTT 3 SEQ ID NO: 1472 -9.3 -21.7 64 -12.4 0 -4.3

ACCAATAGGTGTAAGTCCGT 290 SEQ ID NO: 1473 -9.3 -24.1 68.8 -13.7 -1 -4.7

AACTTATTCCTTCCTCCACG 727 SEQ ID NO: 1474 -9.3 -25.1 69.9 -15.8 0 -3

CTGAGACATGGCTTCTAGCT

818 SEQ ID NO: 1475 -9.3 -24.7 72.7 -13.7 -1-.7 -7.4 AAGTGGCCATATGTTTGGTA

1015 SEQ ID NO: 1476 -9.3 -23.4 68.9 -13.2 -0.5 -9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GGACTCGGGTGAGCTGGTAT 1073 SEQ ID NO: 1477 -9.3 -27.1 77.3 -16.4 -1.3 -5.6

GAATAGCCCATTATGGACTC 1087 SEQ ID NO: 1478 -9.3 -23.2 66.8 -13 -0.8 -5.6

GGCTCACACTTCAAAAGTTC 1162 SEQ ID NO: 1479 -9.3 -21.8 65.1 -11.6 -0.7 -5

CATGATTTTAGCCTGGACTT 1193 SEQ ID NO: 1480 -9.3 -23 67.3 -13.7 0 -4.8

TCGTGCTTGCTTCGGTTAGC 1234 SEQ ID NO: 1481 -9.3 -27.2 77.6 -17.3 -0.3 -5.7

ATGAGGTTGTTGAGGGTGGC 1507 SEQ ID NO: 1482 -9.3 -25.6 76 -16.3 0 -2.8

AAGGTTTTTGACATCTAAAC 1616 SEQ ID NO: 1483 -9.3 -17.4 55.2 -7.4 -0.4 -4.7

TTGTTCCTGGACACCTTCTA 1652 SEQ ID NO: 1484 -9.3 -25.6 73.9 -15.6 -0.5 -6.3

CCCAATCTCTTTTTGTTTTG 1896 SEQ ID NO: 1485 -9.3 -22.5 66.5 -13.2 0 -2.7

TTAAAGCAAGTTTTTAATTA 1979 SEQ ID NO: 1486 -9.3 -14.6 49.2 -4.8 -0.1 -4.3

GATACATCATTTATTTGCTA 2038 SEQ ID NO: 1487 -9.3 -18.8 59 -9.5 0 -3.6

ATCCTCTGGGGCTGTGAAGC 2089 SEQ ID NO: 1488 -9.3 -27.8 79.1 -14.9 -3.6 -10.7

TCTTAACATCATGAACACGA 2561 SEQ ID NO: 1489 -9.3 -18.8 56.8 -9.5 0 -6.9

CCTGCCAGAAATTTTTTATG 2733 SEQ ID NO: 1490 -9.3 -20.8 61 -11.5 0.3 -5.3

TTTCCTTTCTCTTTGCATAG 2892 SEQ ID NO: 1491 -9.3 -22.7 69.1 -13.4 0 -5.2

TACTTTAATATCTTTCCAGG 3002 SEQ ID NO: 1492 -9.3 -19.5 60.3 -10.2 0 -3.3

CTCCCATATTTGTTCTACAG 3092 SEQ ID NO: 1493 -9.3 -23.1 68.3 -13.8 0 -2.9

GATTCTTTGTCCTCCCATAT 3103 SEQ ID NO: 1494 -9.3 -25.5 73.5 -16.2 0 -1.8

CAGCTACCTTTTAAAATTGT 3197 SEQ ID NO: 1495 -9.3 -19.4 58.7 -10.1 0 -6.3

TTAGAAGACATTCTTAGTGA 235 SEQ ID NO: 1496 -9.2 -18.2 58.1 -7.6 -1.3 -6

TTTAAAGACTCTTGTAAATC 268 SEQ ID NO: 1497 -9.2 -15.5 51.3 -6.3 0 -5.3

ACACACGGGACAAAGCTCTT 491 SEQ ID NO: 1498 -9.2 -23.4 66 -14.2 0 -5

GATTTTAGCCTGGACTTGAG 1190 SEQ ID NO: 1499 -9.2 -22.9 67.8 -13.7 0 -4.8

CTCACTCCAGCAGTTCTGAA 1376 SEQ ID NO: 1500 -9.2 -25.2 73.5 -15 -0.9 -5.2

TTGCCCAGTAACCAGGAAGA 1451 SEQ ID NO: 1501 -9.2 -25.4 70.2 -16.2 0 -4

CTTGTTGCCCAGTAACCAGG 1455 SEQ ID NO: 1502 -9.2 -27.1 74.9 -17.2 -0.5 -4.1

GCTATTATGGAATAGTCCAC 1474 SEQ ID NO: 1503 -9.2 -21.5 64.4 -9.9 -2.4 -9.7

TGTTCCTGGACACCTTCTAC 1651 SEQ ID NO: 1504 -9.2 -25.7 74.1 -15.9 -0.3 -6.3

GGGTAGTCGAAGAAGTAGCT 1736 SEQ ID NO: 1505 -9.2 -23.1 68.5 -13.1 -0.6 -5.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GGTTATTATAGGGCACATCC 1815 SEQ ID NO: 1506 -9.2 -23.9 70.4 -14.7 0 -5.1

TTTATTTGCTATTAGTATTT 2029 SEQ ID NO: 1507 -9.2 -17.4 56.8 -8.2 0 -3.6

TTCAAAGGAAGAGGGAGGGG 2348 SEQ ID NO: 1508 -9.2 -22.1 64.6 -12.9 0 -3.4

TAATATTAATTCACACTTAC 2608 SEQ ID NO: 1509 -9.2 -15 50.1 -5.8 0 -5

CTACCTTTTAAAATTGTGAA 3194 SEQ ID NO: 1510 -9.2 -16.8 52.9 -7.6 ^• 0 -6.1

TAATACTTTATTTTAAACAA 3236 SEQ ID NO: 1511 -9.2 -12.5 44.7 -3.3 0 -4.4

GTAAACACTATATCTTATTT 3269 SEQ ID NO: 1512 -9.2 -16.2 53 -7 0 -2.4

CAACATTAGTGACCTGCTGT 20 SEQ ID NO: 1513 -9.1 -23.5 68.2 -14.4 0 -3.6

TACAGTAACCCTTAGTGAAA 119 SEQ ID NO: 1514 -9.1 -20.1 59.9 -9.6 -1.3 -4.6

ACTACAGTAACCCTTAGTGA 121 SEQ ID NO: 1515 -9.1 -22.6 66.5 -12.1 -1.3 -4.6

CAGCACCAATAGGTGTAAGT 294 SEQ ID NO: 1516 -9.1 -22.9 67 -10.5 -3.3 -8.4

TTCCCCATGCGATCGAGCCA 398 SEQ ID NO: 1517 -9.1 -30.7 78.5 -20.9 -0.1 -8.8

GTAATTCACCATTTTAAATT 452 SEQ ID NO: 1518 -9.1 -17 53.8 -7.9 0 -4.5

GAGTAATTCACCATTTTAAA 454 SEQ ID NO: 1519 -9.1 -17.5 54.9 -8.4 0 -4.2

CTTTTATTATTTTGGACTGT 580 SEQ ID NO: 1520 -9.1 -19.1 60.1 -10 0 -3.2

CCAAACTTATTCCTTCCTCC 730 SEQ ID NO: 1521 -9.1 -25.4 70.5 -16.3 0 -1.3

GAGACATGGCTTCTAGCTTA 816 SEQ ID NO: 1522 -9.1 -23.6 70.6 -12.8 -1.7 -7.4

GAAAGTGGCCATATGTTTGG

1017 SEQ ID NO: 1523 -9.1 -22.4 65.3 -12.6 -0.2 -8.5 GGAAAGTGGCCATATGTTTG

1018 SEQ ID NO: 1524 -9.1 -22.4 65.3 -12.6 0 -9 GTCTGGGTACTCAGACTTGA

1049 SEQ ID NO: 1525 -9.1 -24.4 73.6 -11.3 -3.8 -15.4

ATCCATATATGAATAGCCCA 1097 SEQ ID NO: 1526 -9.1 -22.6 64.5 -13 0 -7.5

ATCTGGCTCACACTTCAAAA 1166 SEQ ID NO: 1527 -9.1 -21.4 63.2 -12.3 0 -2.9

TTGAGGCTCATCTGGCTCAC 1175 SEQ ID NO: 1528 -9.1 -26.2 77 -15.8 -1.2 -5.1

AAGAGCTCACTCCAGCAGTT 1381 SEQ ID NO: 1529 -9.1 -25.7 75 -15.1 -1.4 -9.3

TGCCCAGTAACCAGGAAGAT 1450 SEQ ID NO: 1530 -9.1 -25.3 69.8 -16.2 0 -4

GAACTCTCGTTGATCAAACT 1568 SEQ ID NO: 1531 -9.1 -20.2 60.4 -10.2 -0.8 -8.8

AGGTTTTTGACATCTAAACT 1615 SEQ ID NO: 1532 -9.1 -19 59.1 -8.8 -1 -5.6

TGCGGGTAGTTACACATTGT■ 1696 SEQ ID NO: 1533 -9.1 -24 70.1 -14.9 0 -4

GGTTGTAACTTATGCTCTTT 1859 SEQ ID NO: 1534 -9.1 -21.8 66.7 -12.7 0 -4.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo ATTTGCTATTAGTATTTGAT 2026 SEQ ID NO: 1535 -9.1 -18.1 58 -9 0 -3.6

TTATTTGCTATTAGTATTTG 2028 SEQ ID NO: 1536 -9.1 -17.3 56.4 -8.2 0 -3.6

ATCATTTATTTGCTATTAGT 2033 SEQ ID NO: 1537 -9.1 -18.6 59.4 -9.5 0 -3.6

AATTTCTTCATAGTGGAGAT 2210 SEQ ID NO: 1538 -9.1 -19.3 60.6 -9.3 -0.8 -5

TTCAGCTTTACCATGGAGGA 2286 SEQ ID NO: 1539 -9.1 -24.3 70.8 -14.3 -0.6 -8.8

CAGCTGATGCATTCTTGAGA 2316 SEQ ID NO: 1540 -9.1 -23.2 68.7 -12.5 -1.6 -7.6

AATTTCCTATTAGCTGTTTG 2490 SEQ ID NO: 1541 -9.1 -20.4 62.6 -11.3 0 -4.8

TTAATATTAATTCACACTTA 2609 SEQ ID NO: 1542 -9.1 -14.9 49.9 -5.8 0 -7

ATTTCCCTTAATATTAATTC

2616 SEQ ID NO: 1543 -9.1 -17.9 56.1 -8.8 0 -7.3 CATTTCCCTTAATATTAATT

2617 SEQ ID NO: 1544 -9.1 -18.2 56 -9.1 0 -7.3 TAGCTATGGAGCATTTGCTT

2651 SEQ ID NO: 1545 -9.1 -23.4 69.6 -11.8 -2.5 -8.5

CCTCCCATATTTGTTCTACA 3093 SEQ ID NO: 1546 -9.1 -25.1 71.7 -16 0 -2.7

TGTTGATCCACATCTGCACA 3215 SEQ ID NO: 1547 -9.1 -24.6 71 -15.5 3.6 -4.9

TTTGCTATTTTGTTATATCA 3321 SEQ ID NO: 1548 -9.1 -18.7 59.5 -9.6 0 -3.6

AATAATTAAGTACTGTTAAA 3384 SEQ ID NO: 1549 -9.1 -13 45.7 -3.9 0 -6.3

CAGGGCTTCCGTCTCCACTT 374 SEQ ID NO: 1550 -9 -29.9 82.4 -19.6 -1.2 -4

AGTAATTCACCATTTTAAAT 453 SEQ ID NO: 1551 -9 -16.9 53.6 -7.9 0 -4.5

TTTCTCTGTGTTTTGTCAAT 631 SEQ ID NO: 1552 -9 -21.1 66.1 -12.1 0 -2.9

GTTTGGTAACCTTGCAGGCT 1003 SEQ ID NO: 1553 -9 -26.4 75.6 -16.5 -0.8 -6.7

TGGAGAAGAGAGTTTGATCT 1290 SEQ ID NO: 1554 -9 -20.2 62.6 -11.2 0 -5

GATGCTATTATGGAATAGTC 1477 SEQ ID NO: 1555 -9 -19.2 60 -8.3 -1.9 -6.9

TCGTTGATCAAACTGGAGAG 1562 SEQ ID NO: 1556 -9 -20.3 60.8 -10.4 -0.8 -8.7

CAGAGCTCCTAGGGGTTGTA 1872 SEQ ID NO: 1557 -9 -26.8 78.5 -17.1 -0.2 -8.4

CAAGTTTTTAATTAGCGTTA 1973 SEQ ID NO: 1558 -9 -18 56.4 -9 10 -4.1

AATACAAATACCCTGATACA 2052 SEQ ID NO: 1559 -9 -18.5 55.4 -9.5 0 -2.1

TCTTTTATATGGAATCCTCT 2102 SEQ ID NO: 1560 -9 -20.7 63.2 -11.7 0 -6.4

CCGTGTTGGTATCCATCTGT 2147 SEQ ID NO: 1561 -9 -27 76.6 -17.3 -0.4 -4.4

TTTCAGCAACAGTAGCAGAA 2689 SEQ ID NO: 1562 -9 -21.3 64.1 -11.4 -0.7 -4.9

CTTGGATGATGAAAAAGACT 2773 SEQ ID NO: 1563 -9 -16.9 52.9 -7.9 0 -2.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol IntraInter- total duplex Tm of target molecular molecular position oligo inding formation Duplex structure oligo oligo

TGTGTTTAATGTTGTATTTT 2808 SEQ ID NO: 1564 -9 -18.1 58.3 -9.1 0 -2.2

AAAATGTGTTTAATGTTGTA

2812 SEQ ID NO: 1565 -9 -15.7 51.6 -6.7 0 -2.5 CAAAATGTGTTTAATGTTGT

2813 SEQ ID NO: 1566 -9 -16.7 53.4 -7.7 0 -2.5 AGGTCAGTATCACTCTCTTC

3048 SEQ ID NO: 1567 -9 -23.7 74.6 -14.7 0 -2'.3

CACAGCTACCTTTTAAAATT 3199 SEQ ID NO: 1568 -9 -19.1 57.6 -10.1 0 -6.3

AGACTACAGTAACCCTTAGT 123 SEQ ID NO: 1569 -8.9 -22.6 66.9 -13 -0.4 -3.6

GAAGACATTCTTAGTGAAAT 232 SEQ ID NO: 1570 -8.9 -17 54.3 -7 -1 -4.6

CTCCACTTTGGGCAGCATGA 362 SEQ ID NO: 1571 -8.9 -27.3 76.6 -15.9 -2.5 -7.6

ACACTTTATCTCCACACACG 504 SEQ ID NO: 1572 -8.9 -23.1 66.3 -14.2 0 -3

GCTTCTAGCTTCATTCCAAC 688 SEQ ID NO: 1573 -8.9 -24.4 71.9 -14.5 . -0.9 -4.6

TGCTAATGGGGGATGTTACA 963 SEQ ID NO: 1574 -8.9 -23 67 -14.1 0 -3.6

TGAATAGCCCATTATGGACT 1088 SEQ ID NO: 1575 -8.9 -22.8 65.3 -13 -0.8 -5.6

GTTTGATCTGCCATTTTGCA 1279 SEQ ID NO: 1576 -8.9 -24.6 71.7 -15 -0.5 -5.9

CTTCATTTGGTCATCAACCT 1352 SEQ ID NO: 1577 -8.9 -23.3 68.5 -12.7 -1.7 -4.3

TGATGCTATTATGGAATAGT

1478 SEQ ID NO: 1578 -8.9 -18.8 58.5 -8.3 -1.6 -6.9 GTGATGCTATTATGGAATAG

1479 SEQ ID NO: 1579 -8.9 -18.8 58.5 -8.3 -1.6 -4.8 TTCAGCCTGCATACTGATGG

1766 SEQ ID NO: 1580 -8.9 -25 71.7 -14.6 -1.4 -9.5

GTAGAGGTATTCTTCAGCCT 1778 SEQ ID NO: 1581 -8.9 -24.9 75.3 -15.2 -0.6 -4.3

GTAGTAGAGGTATTCTTCAG 1781 SEQ ID NO: 1582 -8.9 -21.1 67.5 -11.6 -0.3 -3.1

ATAGGGCACATCCCCGTTCA 1808 SEQ ID NO: 1583 -8.9 -29.1 78.3 -18.2 -2 -6.4

CATGATTTGGTGGAGCTACC 2435 SEQ ID NO: 1584 -8.9 -24.3 70.4 -14.3 -1 -7

AAAACAACCCTCAGAACATA 2538 SEQ ID NO: 1585 -8.9 -18.8 55.5 -9.9 0 -2.5

AGCCACATTTCAGCAACAGT 2696 SEQ ID NO: 1586 -8.9 -24.6 70.9 -14.9 -0.6 -4.1

TCACTCTCTTCCTTTCCCCT 3039 SEQ ID NO: 1587 -8.9 -29.7 83.3 -20.8 0 0

TGGGAAGGACACATCAGACT 138 SEQ ID NO: 1588 -8.8 -22.7 66.3 -13.2 -0.4 -2.9

TGCAGCTTGTCAAATTTCGT 163 SEQ ID NO: 1589 -8.8 -22.8 66.7 -14 0 -4.9

TTCTTAGTGAAATTATAGGC 225 SEQ .ID NO: 1590 -8.8 -18.1 57.5 -9.3 0 -3.2

TGCATGTTTTCCGGCATCTG 424 SEQ ID NO: 1591 -8.8 -26.2 73.8 -16.7 -0.5 -6.3

CTTTATCTCCACACACGGGA 501 SEQ ID NO: 1592 -8.8 -25 70.3 -16.2 0 -4.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

IntraInter- total duplex Tm of target molecular molecular position oligo 1 inding formation Duplex structure oligo oligo

TGAATTGCAGAGGAAATGGT 865 SEQ ID NO: 1593 -8.8 -19.9 59.6 -11.1 0 -4.9

AGGCAGCATGGTTCAGAGGT 912 SEQ ID NO: 1594 -8.8 -26.8 79 -17.5 -0.2 -5.3

TATATGAATAGCCCATTATG 1092 SEQ ID NO: 1595 -8.8 -19.3 58.1 -10.5 0 -5

CACATAAGCCCAAAGGTGCT 1261 SEQ ID NO: 1596 -8.8 -24.8 68.4 ' -14.6 -1.3 -6.5

CCACTTGTCGGTAAATGTGG 1410 SEQ ID NO: 1597 -8.8 -23.4 66.6 -13.5 -1 -5.2

TACACATTGTGTAGTCCAGC 1686 SEQ ID NO: 1598 -8.8 -23.8 71.3 -13.2 -1.7 -10.8

AAAGCAAGTTTTTAATTAGC 1977 SEQ ID NO: 1599 -8.8 -16.6 53.4 -7.8 0 -4.1

TCATTTATTTGCTATTAGTA 2032 SEQ ID NO: 1600 -8.8 -18.3 58.8 -9.5 0 -3.6

ACATCATTTATTTGCTATTA

2035 SEQ ID NO: 1601 -8.8 -18.3 58 -9.5 0 -3.6 TACATCATTTATTTGCTATT

2036 SEQ ID NO: 1602 -8.8 -18.3 58 -9.5 0 -3.6 TGTGAAGCTTTGATTCACAG

2077 SEQ ID NO: 1603 -8.8 -20.7 63.1 -8.5 -3.4 -9.7

TGGGGCTGTGAAGCTTTGAT 2083 SEQ ID NO: 1604 -8.8 -24.9 71.9 -12.8 -3.3 -8.2

AGGGAGGGGCTATTGTAGGT 2337 SEQ ID NO: 1605 -8.8 -26.4 77.9 -17.6 0 -3.7

AACATATTAATAGAATTTCC 2503 SEQ ID NO: 1606 -8.8 -15.2 50 -6.4 0 -5.9

ACATATTTAAATGGCAAGCT 2523 SEQ ID NO: 1607 -8.8 -18.8 57.2 -9.5 -0.1 -6.4

TTCTTAACATCATGAACACG 2562 SEQ ID NO: 1608 -8.8 -18.3 55.9 -9.5 0 -6.9

CTTGAGGATGTTCAATTGCA 2949 SEQ ID NO: 1609 -8.8 -21.7 64.9 -12.1 -0.6 -6.4

GTAAAAATCACCATTTCCAT 2976 SEQ ID NO: 1610 -8.8 -19.4 57.6 -9.9 -0.4 -2.8

TTTATTTTAAACAAATGTTG 3230 SEQ ID NO: 1611 -8.8 -13.3 46.3 -4 -0.2 -6.4

TTAATACTTTATTTTAAACA 3237 SEQ ID NO: 1612 -8.8 -13.3 46.5 -4.5 0 -4.4

AAAAAATTAAAGTCTAAATG 3441 SEQ ID NO: 1613 -8.8 -9.7 39.1 -0.8 0 -3.2

ACAGTAACCCTTAGTGAAAG 118 SEQ ID NO: 1614 -8.7 -20.4 60.6 -10.3 -1.3 -4.6

AATCATTGAGCAAAAGAAAA

184 SEQ ID NO: 1615 -8.7 -14 46.8 -5.3 0 -4.5 AAATCATTGAGCAAAAGAAA

185 SEQ ID NO: 1616 -8.7 -14 46.8 -5.3 10 -4.5 GAAATCATTGAGCAAAAGAA

186 SEQ ID NO: 1617 -8.7 -15.3 49.5 -6.6 0 -4.5 TCTCCACTTTGGGCAGCATG

363 SEQ ID NO: 1618 -8.7 -27.1 77 -15.9 -2.5 -7.1

TTGCATGTTTTCCGGCATCT

425 SEQ ID NO : 1619 -8.7 -26.3 74.4 -16.7 -0.7 -6.3

GGTTTTCTATACATGTGTAC

600 SEQ ID NO : 1620 -8.7 -20.6 64.6 -11.9 0 -7.1

TAAGGACAACGCTTTCTCTG

643 SEQ ID NO : 1621 -8.7 -21.5 63.2 -12.8 0 -3.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol IntraInter- total duplex Tm of target molecular molecular position oligo ] inding formation Duplex structure oligo oligo

CAGCTTCTAGCTTCATTCCA 690 SEQ ID NO: 1622 -8.7 -25.6 75.3 -15.1 -1.8 -6

GATCACCTGAGACATGGCTT 824 SEQ ID NO: 1623 -8.7 -24.9 71.4 -16.2 0 -5.2

CACTTCAAAAGTTCCAGTAT 1156 SEQ ID NO: 1624 -8.7 -20.2 61 -10.6 -0.7 -4.2

GACTTGAGGCTCATCTGGCT 1178 SEQ ID NO: 1625 -8.7 -26.6 77.5 -17 -0.8 -5

TTGCTTCGGTTAGCCTGCTC 1228 SEQ ID NO: 1626 -8.7 -28.1 80 -18.5 -0.7 -5.3

TAAGAGCTCACTCCAGCAGT 1382 SEQ ID NO: 1627 -8.7 -25.3 74 -15.1 -1.4 -9.3

ATACATCATTTATTTGCTAT 2037 SEQ ID NO: 1628 -8.7 -18.2 57.6 -9.5 0 -3.6

GTTTGCAATACAAATACCCT 2058 SEQ ID NO: 1629 -8.7 -21.2 61.3 -10.8 -1.7 -7.4

AGTTCAGCTTTACCATGGAG 2288 SEQ ID NO: 1630 -8.7 -23.7 70.4 -14.3 0 -8.8

ATAGAATTTCCTATTAGCTG 2494 SEQ ID NO: 1631 -8.7 -19.3 59.8 -10.6 0 -6.4

ATTTCAGCAACAGTAGCAGA 2690 SEQ ID NO: 1632 -8.7 -22 66.3 -12.3 -0.9 -4.5

GAGGATGTTCAATTGCAGCA 2946 SEQ ID NO: 1633 -8.7 -23.2 68.4 -14.5 0 -6.4

CGATTCTTTGTCCTCCCATA 3104 SEQ ID NO: 1634 -8.7 -26.3 73.4 -17.6 0 -2.1

TTAAAGTCTAAATGAGATTC 3435 SEQ ID NO: 1635 -8.7 -14.9 50 -5.6 -0.3 -3.7

TAAACCATGTATCCAGTTTC 1 SEQ ID NO: 1636 -8.6 -21 62.8 -11.8 -0.3 -4.3

TCTGTACTTTTTCCAACATT

33 SEQ ID NO: 1637 -8.6 -21.1 63.9 -12.5 0 -4.8 CTCTGTACTTTTTCCAACAT

34 SEQ ID NO: 1638 -8.6 -21.9 65.5 -13.3 0 -4.8 ATTAGAAGACATTCTTAGTG

236 SEQ ID NO: 1639 -8.6 -17.6 56.7 -7.6 -1.3 -6

TTTTATTATTTTGGACTGTT 579 SEQ ID NO: 1640 -8.6 -18.3 58.4 -9.7 0 -3.4

TTCAGGGCCCTGTCTCTCTT 760 SEQ ID NO: 1641 -8.6 -29.5 85.1 -17.1 -0.3 -15.8

CTTAAGTCCATTGGCTCGGA 800 SEQ ID NO: 1642 -8.6 -25.3 71.6 -16.2 -0.2 -6.6

AGACATGGCTTCTAGCTTAA 815 SEQ ID NO: 1643 -8.6 -22.3 66.8 -12 -1.7 -7.4

CCTGAGACATGGCTTCTAGC 819 SEQ ID NO: 1644 -8.6 -25.8 74.4 -16.2 -0.9 -6.7

CATATGTTTGGTAACCTTGC 1008 SEQ ID NO: 1645 -8.6 -22.2 65.6 -13.6 0.1 -5

GAGCTCGTCTGGTAACTATC 1114 SEQ ID NO: 1646 -8.6 -23.6 70.4 -14.4 0 -8.6

CAAACTGGAGAGAACGAAGT 1554 SEQ ID NO: 1647 -8.6 -18.8 56.2 -9.5 -0.5 -3.5

TTTGACATCTAAACTAAAGA 1610 SEQ ID NO: 1648 -8.6 -15.3 50.2 -6.7 0 -2.8

TAGTCGAAGAAGTAGCTGTC 1733 SEQ ID NO: 1649 -8.6 -21.1 64.6 -11.7 -0.6 -5.8

CATCATTTATTTGCTATTAG 2034 SEQ ID NO: 1650 -8.6 -18.1 57.6 -9.5 0 -3.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GTCTAAGTTGCTTTAGCTAT

2664 SEQ ID NO: 1651 -8.6 -21.8 67.5 -11.8 -1.3 -6.5 GATGAAAAAGACTGATGTAT

2766 SEQ ID NO: 1652 -8.6 -15.6 50.5 -7 0 -2.4 AGAACTGTGACTATTTGACA

2839 SEQ ID NO: 1653 -8.6 -19.3 59.5 -10.7 0 -3.3 TAGAACTGTGACTATTTGAC

2840 SEQ ID NO: 1654 -8.6 -18.3 57.6 -9.7 0 -3.4 TCCAACTACTTAGAACTGTG

2850 SEQ ID NO: 1655 -8.6 -20.3 61.1 -11.7 0 -3.3 TCAGTATCACTCTCTTCCTT

3045 SEQ ID NO: 1656 -8.6 -24.3 74.1 -15.7 0 -2.5 CATATTTGTTCTACAGCAGA

3088 SEQ ID NO: 1657 -8.6 -20.9 64.2 -12.3 0 -4.1 CATCGCATGTTAATAATACT

3148 SEQ ID NO: 1658 -8.6 -18.5 56.4 -9.9 0 -5.1 AGCTACCTTTTAAAATTGTG

3196 SEQ ID NO: 1659 -8.6 -18.7 57.4 -10.1 0 -6.3 AAATGTTGATCCACATCTGC

3218 SEQ ID NO: 1660 -8.6 -21.6 63.7 -12.2 -0.6 -4.9 ACGACATAGAATAATTAAGT

3393 SEQ ID NO: 1661 -8.6 -15.4 50 -6.8 0 -4.5 CCAACATTAGTGACCTGCTG

21 SEQ ID NO: 1662 -8.5 -24.3 68.6 -15.8 0 -3.6 TGGTTTTCTATACATGTGTA

601 SEQ ID NO: 1663 -8.5 -20.4 ^■63.9 -11.9 0 -7.1 TTGAAAACGACAGTAAGGAC

656 SEQ ID NO: 1664 -8.5 -17.3 53.4 -8.8 0 -3.5 ATCACCTGAGACATGGCTTC

823 SEQ ID NO: 1665 -8.5 -24.7 71.7 -16.2 0 -5.2 TCTGGGTACTCAGACTTGAT

1048 SEQ ID NO: 1666 -8.5 -23.2 69.9 -12.7 -1.8 -11.4 GAGCTGGTATAGGGGTCTGG

1063 SEQ ID NO: 1667 -8.5 -26.4 78.1 -17.9 0 -5 GCTTTTCGTGCTTGCTTCGG

1239 SEQ ID NO: 1668 -8.5 -27.4 77.1 -18.9 0 -5.7 TTTGCACATAAGCCCAAAGG

1265 SEQ ID NO: 1669 -8.5 -22.9 64.3 -13.9 -0.1 -5 ACCAGGAAGATGGATCCTTC

1441 SEQ ID NO: 1670 -8.5 -24.2 69.4 -14.3 -1.3 -9.1 ACTGGAGAGAACGAAGTTTT

1551 SEQ ID NO: 1671 -8.5 -19.8 59.6 -9.5 -1.8 -6 AGACATACGAACTCTCGTTG

1576 SEQ ID NO: 1672 -8.5 -21 61.8 -10.2 -2.3 -6.5 CTGGAAGTTTTCAAGGTTTT

1628 SEQ ID NO: 1673 -8.5 -20.6 63.2 -11.2 -0.8 -3.8 CTTGTAGTAGAGGTATTCTT

1784 SEQ ID NO: 1674 -8.5 -21 66.6 -12 -0.1 -2.7 CTCCTAGGGGTTGTAACTTA

1867 SEQ ID NO: 1675 -8.5 -23.9 70.6 -14.7 -0.2 -8.6 GAGGGAGGGGCTATTGTAGG

2338 SEQ ID NO: 1676 -8.5 -25.8 75.6 -17.3 0 -3.7 GTATACTAACAAGACTTCCT

2750 SEQ ID NO: 1677 -8.5 -20 60.7 -11.5 0 -5.5 AACTGTGACTATTTGACATC

2837 SEQ ID NO: 1678 -8.5 -19.1 59.3 -10.6 0 -3.3 ATTGCAGCAAGAATGAACCT

2935 SEQ ID NO: 1679 -8.5 -21.3 61.7 -12.1 0 -8.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

IntraInter- total duplex Tm of target molecular molecular position oligo i inding formation Duplex structure oligo oligo

TGTAAAAATCACCATTTCCA 2977 SEQ ID NO: 1680 -8.5 -19.4 57.6 -10.9 0.1 -2.8

TCCTCCCATATTTGTTCTAC 3094 SEQ ID NO: 1681 -8.5 -24.8 72.2 -16.3 0 -2.1

ATAAGGCAAGACTTTCATAC 3174 SEQ ID NO: 1682 -8.5 -18.9 58.5 -10.4 0 -3.2

GCTACCTTTTAAAATTGTGA 3195 SEQ ID NO: 1683 -8.5 -19.3 58.5 -10.8 0 -6:3

GCACAGCTACCTTTTAAAAT 3200 SEQ ID NO: 1684 -8.5 -20.8 61.1 -12.3 0 -6.3

ACATCTGCACAGCTACCTTT 3206 SEQ ID NO: 1685 -8.5 -25.3 72.8 -16.2 -0.3 -4.6

TCACGACATAGAATAATTAA 3395 SEQ ID NO: 1686 -8.5 -15.3 49.7 -6.8 0 -4.5

TGACCTGCTGTAAACCATGT

11 SEQ ID NO: 1687 -8.4 -24 67.7 -15.6 0 -4.3 GTGACCTGCTGTAAACCATG

12 SEQ ID NO: 1688 -8.4 -24 67.7 -15.6 0 -3.9 AGTGACCTGCTGTAAACCAT

13 SEQ ID NO: 1689 -8.4 -24 68.1 -15.6 . 0 -3.6 CAAAAGAAAAGTGCAGCTTG

174 SEQ ID NO: 1690 -8.4 -17.6 54 -8.5 -0.4 -7

TGAAAACGACAGTAAGGACA

655 SEQ ID NO: 1691 -8.4 -17.9 54.3 -8.8 -0.4 -3.9

TTTGAAAACGACAGTAAGGA

657 SEQ ID NO: 1692 -8.4 -17.2 53.2 -8.8 0 -3.5

GATGGCCCGGCTAGGAAAGT

1031 SEQ ID NO: 1693 -8.4 -27.6 74.1 -18.5 -0.4 -8.1 TGATGGCCCGGCTAGGAAAG

1032 SEQ ID NO: 1694 -8.4 -26.4 70.9 -17.5 -0.2 -7.3 CTTGATGGCCCGGCTAGGAA

1034 SEQ ID NO: 1695 -8.4 -28.1 74.9 -19 -0.4 -8.1

GCATTGACTTGTTCCTGGAC 1660 SEQ ID NO: 1696 -8.4 -25 72.7 -16.6 0 -7

ACACATTGTGTAGTCCAGCA 1685 SEQ ID NO: 1697 -8.4 -24.8 73.1 -14.9 -1.4 -9.9

TACTTTTTTTCTTCCTGTTC 1936 SEQ ID NO: 1698 -8.4 -21.8 67.9 -13.4 0 -2.2

TAGTATTTGATTATTATGCC 2017 SEQ ID NO: 1699 -8.4 -18.8 59 -10.4 0 -3

ATTTATTTGCTATTAGTATT 2030 SEQ ID NO: 1700 -8.4 -17.3 56.4 -8.9 0 -3.6

TGTTCATGATTTGGTGGAGC 2439 SEQ ID NO: 1701 -8.4 -23.2 69.9 -14.8 0 -6.4

ACACTCAAATTAGGCTGTTC 2454 SEQ ID NO: 1702 -8.4 -21.1 63.9 -12.7 0 -3.7

AAGGTCTAAGTTGCTTTAGC 2667 SEQ ID NO: 1703 -8.4 -21.7 66.6 -12.6 -0.5 -5.5

AATGAACCTTGAGTCAATAC 2924 SEQ ID NO: 1704 -8.4 -18.5 56.7 -9.6 0 -7.6

GATCCACATCTGCACAGCTA 3211 SEQ ID NO: 1705 -8.4 -25.7 73.6 -16.7 -0.3 -4.9

AGGTGTAAGTCCGTGCTTTA 284 SEQ ID NO: 1706 -8.3 .-24.8 72.6 -15.8 -0.4 -4.3

ATTCACCATTTTAAATTGAG 449 SEQ ID NO: 1707 -8.3 -17.4 54.7 -9.1 0 -5.4

AAGTCCATTGGCTCGGATGA 797 SEQ ID NO: 1708 -8.3 -25.2 71 -16.2 -0.4 -6.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTGATGGCCCGGCTAGGAAA 1033 SEQ ID NO: 1709 -8.3 -26.5 70.9 -17.5 -0.4 -8.1

GGCCATGATTTTAGCCTGGA 1196 SEQ ID NO: 1710 -8.3 -26.8 74.8 -17.2 -1.2 -7

TCATTTGGTCATCAACCTTA 1350 SEQ ID NO: 1711 -8.3 -22.1 65.9 -12.1 -1.7 -4.3

CCAAGAATTTCAGACATACG 1587 SEQ ID NO: 1712 -8.3 -19.4 57.6 -11.1 0 -5.1

CACCTTCTACCAGCTGGAAG 1641 SEQ ID NO: 1713 -8.3 -25.6 71.9 -15 -0.7 -12.7

TAGGGCACATCCCCGTTCAG 1807 SEQ ID NO: 1714 -8.3 -29.1 78.7 -18.8 -2 -6.4

CCTCCCCACTCCCCCAATCT 1908 SEQ ID NO: 1715 -8.3 -34.8 86.1 -26.5 0 -1.1

CCACTCCATTACAATGTCTT 2118 SEQ ID NO: 1716 -8.3 -23.5 67.7 -15.2 0 -5.1

TCTGACCGTGTTGGTATCCA

2152 SEQ ID NO: 1717 -8.3 -26.6 75.1 -16.7 -1.5 -5 TTCTGACCGTGTTGGTATCC

2153 SEQ ID NO: 1718 -8.3 -26 74.4 -16.7 -0.9 -4.5 GCTCAAATCCCCCGCTGTAT

2257 SEQ ID NO: 1719 -8.3 -29.2 76.4 -20.9 0 -3.3 AGCTCAAATCCCCCGCTGTA

2258 SEQ ID NO: 1720 -8.3 -29.2 76.7 -20.9 0 -4.3 TCAGCTTTACCATGGAGGAA

2285 SEQ ID NO: 1721 -8.3 -23.5 68.1 -14.3 -0.6 -8.8

GAATTGTTTCAGTTCAGCTT 2298 SEQ ID NO: 1722 -8.3 -21.7 67 -12.5 -0.7 -5.9

GTGGCTGACACAGGTCCATT 2408 SEQ ID NO: 1723 -8.3 -27.1 77.5 -17.2 -1.5 -8.4

TATTAATAGAATTTCCTATT 2499 SEQ ID NO: 1724 -8.3 -15.7 51.6 -6.6 -0.6 -5.5

ACCCTCAGAACATATTTAAA 2532 SEQ ID NO: 1725 -8.3 -19.2 57.4 -10.9 0 -4.6

AAACAACCCTCAGAACATAT 2537 SEQ ID NO: 1726 -8.3 -19.5 57.2 -11.2 0 -2.5

TGAACACGAGACAAAACAAC 2550 SEQ ID NO: 1727 -8.3 -16.2 50.4 -7.9 0 -3.5

ATGTGTTTAATGTTGTATTT 2809 SEQ ID NO: 1728 -8.3 -18 58 -9.7 0 -2.5

GTCAATTTTGTTTCCAACTA 2862 SEQ ID NO: 1729 -8.3 -20.5 62.4 -11.5 -0.5 -4

CTTTCATACCTGTGGCATCG 3163 SEQ ID NO: 1730 -8.3 -25.1 71.3 -16.8 0 -4

ACAGCTACCTTTTAAAATTG 3198 SEQ ID NO: 1731 -8.3 -18.4 56.3 -10.1 0 -6.3

ATGTAAACACTATATCTTAT 3271 SEQ ID NO: 1732 -8.3 -16 52.3 -7.7 10 -4.2

AACATTAAGGAAATTACCGC 3342 SEQ ID NO: 1733 -8.3 -18.3 54.8 -9.3 -0.5 -3.7

AAAAATTAAAGTCTAAATGA 3440 SEQ ID NO: 1734 -8.3 -11 41.5 -2.7 0 -3.2

CTTTCCCTGGACTCTGTACT 45 SEQ ID NO: 1735 -8.2 -26.6 76.4 -18.4 0 -4.8

CTACAGTAACCCTTAGTGAA 120 SEQ ID NO: 1736 -8.2 -21.7 63.8 -12.1 -1.3 -4.6

ACATTCTTAGTGAAATTATA 228 SEQ ID NO: 1737 -8.2 -16 52.5 -7.1 -0.4 -3.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

IntraInter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AGCTTCTAGCTTCATTCCAA 689 SEQ ID NO: 1738 -8.2 -24.2 71.6 -14.3 -1.7 -5.8

CATAGCTTGGATCACCTGAG 833 SEQ ID NO: 1739 -8.2 -23.8 69.2 -14.6 -0.9 -6.8

ATCAAACTGGAGAGAACGAA 1556 SEQ ID NO: 1740 -8.2 -18 54.6 -9.8 0 -3.5

CGTTGATCAAACTGGAGAGA 1561 SEQ ID NO: 1741 -8.2 -20.5 60.7 -11.3 -0.8 -9.4

GCTTGTAGTAGAGGTATTCT 1785 SEQ ID NO: 1742 -8.2 -22.7 71.1 -14.5 0 -3.8

GTTCAATCCACTCCATTACA 2125 SEQ ID NO: 1743 -8.2 -23.7 68.6 -15.5 0 -2

CTGACACAGGTCCATTAGTA 2404 SEQ ID NO: 1744 -8.2 -23.5 69.6 -13.9 -1.3 -4.3

TAAATGGCAAGCTAACATAT 2516 SEQ ID NO: 1745 -8.2 -17.6 54.3 -9.4 0 -5.5

TCCCTTAATATTAATTCACA 2613 SEQ ID NO: 1746 -8.2 -19.3 58.4 -11.1 0 -7.3

AGCATTTGCTTTGAAAGTTT 2642 SEQ ID NO: 1747 -8.2 -20.2 61.7 -11.3 -0.4 -7.6

AGTTGCTTTAGCTATGGAGC 2659 SEQ ID NO: 1748 -8.2 -23.9 72.2 -14.2 -1.4 -8.2

CTAAGTTGCTTTAGCTATGG 2662 SEQ ID NO: 1749 -8.2 -21.4 65.1 -11.8 -1.3 -6.5

ATCCAACΑATGCCAAAGCCA 2711 SEQ ID NO: 1750 -8.2 -24.2 65.5 -15.1 -0.7 -3.2

GAAATTTTTTATGAAATCCA 2726 SEQ ID NO: 1751 -8.2 -15.7 50.6 -7 -0.1 -6

AGACTTTCATACCTGTGGCA 3166 SEQ ID NO: 1752 -8.2 -24.7 71.9 -16.5 0 -4

GTGAAATAAGGCAAGACTTT 3179 SEQ ID NO: 1753 -8.2 -18.3 56.3 -10.1 0 -4

TACCTTTTAAAATTGTGAAA 3193 SEQ ID NO: 1754 -8.2 -15.2 49.5 -7 0 -6.7

TAGTGACCTGCTGTAAACCA 14 SEQ ID NO: 1755 -8.1 -23.7 67.6 -15.6 0 -3.6

GCATCTGGCCCTGTTCCCCA 411 SEQ ID NO: 1756 -8.1 -34.1 89.3 -26 0 -6.6

GCATGTTTTCCGGCATCTGG 423 SEQ ID NO: 1757 -8.1 -27.4 76.6 -18.7 -0.3 -6.3

CCTTACAGCTTCTAGCTTCA 695 SEQ ID NO: 1758 -8.1 -25.3 74.5 -15.4 -1.8 -6

GTAACCTTGCAGGCTGCCGT 998 SEQ ID NO: 1759 -8.1 -29.6 79.8 -19.9 -1.4 -10.1

TATCCATATATGAATAGCCC 1098 SEQ ID NO: 1760 -8.1 -21.6 62.8 -13 0 -7.5

CTCTTGCTGCAAATAGGCCA 1211 SEQ ID NO: 1761 -8.1 -25.5 71.5 -16.6 0 -9.3

GATCTGCCATTTTGCACATA 1275 SEQ ID NO: 1762 -8.1 -23.8 68.9 -14.9 -0.6 -5.4

TGCTATTATGGAATAGTCCA 1475 SEQ ID NO: 1763 -8.1 -21.3 63.8 -11 -2.2 -9.4

GTCTGCTGCGGGTAGTTACA 1702 SEQ ID NO: 1764 -8.1 -27 78.3 -18.9 0 -7.3

TAGCTGTCCAAATTTCTCTG 1721 SEQ ID NO: 1765 -8.1 -22.1 66.1 -14 0 -4.8

TGGCATGCAACATTTCAATG 1839 SEQ ID NO: 1766 -8.1 -21 61.6 -11.8 0 -10.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GTACTTTTTTTCTTCCTGTT 1937 SEQ ID NO: 1767 -8.1 -22.6 69.8 -14.5 0 -4

GGAATCCTCTGGGGCTGTGA 2092 SEQ ID NO: 1768 -8.1 -27.8 78.3 -19.7 0.2 -5.6

TTCAGTTCAGCTTTACCATG 2291 SEQ ID NO: 1769 -8.1 -23.1 69.3 -15 0 -4.6

TGAGAATTGTTTCAGTTCAG 2301 SEQ ID NO: 1770 -8.1 -19.5 61.5 -9.8 -1.5 -5.8

AAATTAGGCTGTTCATGATT 2448 SEQ ID NO: 1771 -8.1 -19.4 59.7 -11.3 0 -6.4

ATTTCCTATTAGCTGTTTGC 2489 SEQ ID NO: 1772 -8.1 -22.9 69.2 -14.1 -0.4 -4.8

ATGAACACGAGACAAAACAA 2551 SEQ ID NO: 1773 -8.1 -16 50 -7.9 0 -3.5

TTCCCTTAATATTAATTCAC 2614 SEQ ID NO: 1774 -8.1 -18.7 57.5 -10.6 0 -7.1

TTAGCTATGGAGCATTTGCT 2652 SEQ ID NO: 1775 -8.1 -23.4 69.6 -12.8 -2.5 -8.3

TTCAGCAACAGTAGCAGAAA 2688 SEQ ID NO: 1776 -8.1 -20.5 61.6 -11.4 -0.9 -5

TCATCCTTTCCTTTCTCTTT 2898 SEQ ID NO: 1777 -8.1 -24.9 74.4 -16.8 0 -0.5

ATTTGCGATTCTTTGTCCTC 3109 SEQ ID NO: 1778 -8.1 -23.9 70.5 -15.8 0 -4.1

TGTGAAATAAGGCAAGACTT

3180 SEQ ID NO: 1779 -8.1 -18.2 55.9 -10.1 0 -4 TTGTGAAATAAGGCAAGACT

3181 SEQ ID NO: 1780 -8.1 -18.2 55.9 -10.1 0 -4 GAAATTACCGCTTTTGCTAT

3333 SEQ ID NO: 1781 -8.1 -21.4 61.9 -11.7 -1.5 -5.5

CGACATAGAATAATTAAGTA 3392 SEQ ID NO: 1782 -8.1 -14.9 49.1 -6.8 0 -4.5

CACGACATAGAATAATTAAG 3394 SEQ ID NO: 1783 -8.1 -14.9 48.7 -6.8 0 -4.5

AAAAAAATTAAAGTCTAAAT 3442 SEQ ID NO: 1784 -8.1 -9 37.9 -0.8 0 -3

AAGCAAGTCTTTCCCTGGAC 53 SEQ ID NO: 1785 -8 -25.1 71.8 -16.6 -0.2 -5

CTCCACGCATTCGGTCGGCC 714 SEQ ID NO: 1786 -8 -31.4 81.1 -23.4 0 -6.8

GTACATTGGCCCAAACTTAT 740 SEQ ID NO: 1787 -8 -23.1 65.6 -15.1 0 -6.6

CCTTTGGAGGCAGAGTGGAT 889 SEQ ID NO: 1788 -8 -26.2 75.1 -17.5 -0.5 -4.5

GGTAGGCCTTTGGAGGCAGA 895 SEQ ID NO: 1789 -8 -28.3 80.6 -16.7 -3.6 -9.1

ATGAATAGCCCATTATGGAC 1089 SEQ ID NO: 1790 -8 -21.9 63.4 -13 -0.8 -5.6

GCAGCTTCATTTGGTCATCA 1356 SEQ ID NO: 1791 -8 -25.2 75 -17.2 0 -4.5

AGCAGTTCTGAAGCAGCTTC 1368 SEQ ID NO: 1792 -8 -24.7 74.2 -15.1 -0.9 -11.1

CCCCAATCTCTTTTTGTTTT 1897 SEQ ID NO: 1793 -8 -24.5 70.3 -16.5 0 -2.7

ACTCCCCCAATCTCTTTTTG 1901 SEQ ID NO: 1794 -8 -26.5 73.5 -18.5 0 -2.5

TAAAGCAAGTTTTTAATTAG 1978 SEQ ID NO: 1795 -8 -14.5 49 -6.5 0 -5.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CTTCTGACCGTGTTGGTATC 2154 SEQ ID NO: 1796 -8 -24.9 72.7 -15.3 -1.5 -4.5

TCATAGTGGAGATCAGTTTA 2203 SEQ ID NO: 1797 -8 -20.6 64.7 -12.6 0 -5.4

TAAGCTCAAATCCCCCGCTG 2260 SEQ ID NO: 1798 -8 -27.3 71.5 -18.7 -0.3 -5

TTAATGTTGTATTTTTAAAT 2803 SEQ ID NO: 1799 -8 -14 48.1 -6 0 -4. '5

TTGCAGCAAGAATGAACCTT 2934 SEQ ID NO: 1800 -8 -21.4 62 -12.9 0 -7.9

TTGAGGATGTTCAATTGCAG 2948 SEQ ID NO: 1801 -8 -20.8 63.1 -12.1 -0.4 -8

AGAATTCATAAAGTTACAAG 70 SEQ ID NO: 1802 -7.9 -14.6 49 -6.7 0 -7.4

CCCTTAGTGAAAGTTAAGAA 111 SEQ ID NO: 1803 -7.9 -19.3 58.1 -10.9 -0.2 -4.8

TCCGTGTCGGTCCGGAAGCC 314 SEQ ID NO: 1804 -7.9 -31.3 81.2 -21.4 -1.9 -11.4

CCCAGGGCTTCCGTCTCCAC 376 SEQ ID NO: 1805 -7.9 -32.9 86.8 -23.7 -1.2 -5.9

TTCACCATTTTAAATTGAGA 448 SEQ ID NO: 1806 -7.9 -18 55.9 -10.1 0 -4.9

TTTTGAAAACGACAGTAAGG 658 SEQ ID NO: 1807 -7.9 -16.7 52.3 -8.8 0 -3.5

GTCGGCCCTTACAGCTTCTA 701 SEQ ID NO: 1808 -7.9 -28.8 80.2 -20.2 -0.4 -6.2

CTGTCTCTCTTGTACATTGG 751 SEQ ID NO: 1809 -7.9 -23.2 71 -15.3 0 -6.3

CTCGGATGAGGGCTTTTTTC 786 SEQ ID NO: 1810 -7.9 -24.5 71.5 -15.8 -0.6 -6.1

GTTTTGAATTGCAGAGGAAA 869 SEQ ID NO: 1811 -7.9 -19 58.2 -11.1 0 -5.3

GAAGTTTTGCCACTAACTCC 1539 SEQ ID NO: 1812 -7.9 -23.5 67.8 -14.9 -0.5 -3.7

TCAGGTGCTTGTAGTAGAGG 1791 SEQ ID NO: 1813 -7.9 -23.9 73.5 -16 0 -3.7

CAAATACCCTGATACATCAT 2048 SEQ ID NO: 1814 -7.9 -20.4 59.5 -12.5 0 -5

TGGTATCCATCTGTGAGTTC 2141 SEQ ID NO: 1815 -7.9 -24 72.9 -15.6 -0.2 -4

TACAAGAACCGTTCTGTCCG 2179 SEQ ID NO: 1816 -7.9 -23.8 66.2 -14.9 -0.9 -8.9

AAATTTCTTCATAGTGGAGA 2211 SEQ ID NO: 1817 -7.9 -18.6 58.5 -10.1 -0.3 -5

CCTTCAAAGGAAGAGGGAGG 2350 SEQ ID NO: 1818 -7.9 -22.6 65.1 -12.7 -2 -5.9

ATGATTTGGTGGAGCTACCA 2434 SEQ ID NO: 1819 -7.9 -24.3 70.4 -14.3 -2.1 -9.6

CATGAACACGAGACAAAACA 2552 SEQ ID NO: 1820 -7.9 -17.4 52.6 -9.5 0 -3.7

GTTGCTTTAGCTATGGAGCA 2658 SEQ ID NO: 1821 -7.9 -24.6 73.1 -14.2 -2.5 -10.4

TGAAAAAGACTGATGTATAC 2764 SEQ ID NO: 1822 -7.9 -14.9 49.3 -7 0 -5.3

CCTAGCAAAATGTGTTTAAT • 2818 SEQ ID NO: 1823 -7.9 -18.6 56.6 -10.7 0 -4.1

CTCTTGAGGATGTTCAATTG 2951 SEQ ID NO: 1823 -7.9 -20.5 62.9 -11.8 -0.6 -6.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AAGGTCAGTATCACTCTCTT 3049 SEQ ID NO: 1825 -7.9 -22.6 70 -14.7 0 -2.5

AATTTGCGATTCTTTGTCCT 3110 SEQ ID NO: 1826 -7.9 -22.8 66.6 -14.9 0 -3.4

CATGTTAATAATACTGATAA 3143 SEQ ID NO: 1827 -7.9 -14.4 48.4 -6.5 0 -3.5

ATCGCATGTTAATAATACTG 3147 SEQ ID NO: 1828 -7.9 -17.8 55.2 -9.9 0 -5:2

AATTGTGAAATAAGGCAAGA 3183 SEQ ID NO: 1829 -7.9 -16.4 51.9 -7.6 -0.8 -4.8

ATGTTGATCCACATCTGCAC 3216 SEQ ID NO: 1830 -7.9 -23.9 69.8 -15.5 -0.1 -4.1

TTATTTTAAACAAATGTTGA 3229 SEQ ID NO: 1831 -7.9 -13.8 47.2 -5.2 -0.4 -6.4

TAAAGTCTAAATGAGATTCC 3434 SEQ ID NO: 1832 -7.9 -16.8 53.6 -8.9 0.2 -4.1'

GGTGTAAGTCCGTGCTTTAA 283 SEQ ID NO: 1833 -7.8 -24.1 69.9 -16.3 0.1 -3.6

CCCTTACAGCTTCTAGCTTC 696 SEQ ID NO: 1834 -7.8 -26.6 77.1 -17 -1.8 -6

TAGGCCTTTGGAGGCAGAGT 893 SEQ ID NO: 1835 -7.8 -27.1 78.2 -14.9 -4.4 -9.9

GCTAATGGGGGATGTTACAA 962 SEQ ID NO: 1836 -7.8 -22.3 65 -14.5 0 -3.1

TTTGGTAACCTTGCAGGCTG 1002 SEQ ID NO: 1837 -7.8 -25.2 72 -16.5 -0.8 -6.7

CCATGATTTTAGCCTGGACT 1194 SEQ ID NO: 1838 -7.8 -24.9 70.6 -17.1 0 -4.8

AGCCTGCTCTTGCTGCAAAT 1217 SEQ ID NO: 1839 -7.8 -26.6 74.4 -16.5 -2.3 -9.3

TCGACAATGGAGAAGAGAGT 1297 SEQ ID NO: 1840 -7.8 -20.1 60.2 -12.3 0 -4.2

GCCCACTCGACAATGGAGAA 1303 SEQ ID NO: 1841 -7.8 -25.3 68.5 -16.7 -0.6 -5.8

ACTACTCCTGGCCCACTCGA 1313 SEQ ID NO: 1842 -7.8 -29.8 79.5 -22 0 -6.6

GTAACCAGGAAGATGGATCC 1444 SEQ ID NO: 1843 -7.8 -23 66.1 -14.1 -1 -7.5

TTGTTGCCCAGTAACCAGGA 1454 SEQ ID NO: 1844 -7.8 -26.8 74.3 -18.3 -0.5 -4.2

GGTACAGCTGATGCATTCTT 2320 SEQ ID NO: 1845 -7.8 -24.3 72 -14.9 -1.6 -9.1

GGCAGAGGTGCTCGGGCCTT 2366 SEQ ID NO: 1846 -7.8 -31.8 86.9 -21.3 -2.7 -11.2

ATTAATAGAATTTCCTATTA 2498 SEQ ID NO: 1847 -7.8 -15.7 51.6 -6.6 -1.2 -6.7

CCTGCATTTTCTTAACATCA 2570 SEQ ID NO: 1848 -7.8 -22.1 65.2 -14.3 0 -4.9

AATTTTTTATGAAATCCAAC 2724 SEQ ID NO: 1849 -7.8 -15.3 49.9 -7 -0.1 -3.9

TAAAAATCACCATTTCCATC 2975 SEQ ID NO: 1850 -7.8 -18.6 56.1 -10.1 -0.4 -2.8

AGTCATTTGAAGAATTTGCG 3122 SEQ ID NO: 1851 -7.8 -19.1 58.2 -11.3 0 -4.8

TAAATCCCCAGTATCTGAAT• 254 SEQ ID NO: 1852 -7.7 -21.5 62.2 -13.2 -0.3 -4.1

GAAAACGACAGTAAGGACAA 654 SEQ ID NO: 1853 -7.7 -17.2 52.7 -8.8 -0.4 -3.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTGAATTGCAGAGGAAATGG 866 SEQ ID NO: 1854 -7.7 -18.8 57 -11.1 0 -5.2

GGCCATATGTTTGGTAACCT 1011 SEQ ID NO: 1855 -7.7 -25.3 71.6 -16.9 -0.5 -7.4

CTGGCCCACTCGACAATGGA 1306 SEQ ID NO: 1856 -7.7 -27.5 73.1 -19.3 -0.1 -6.6

GCAGTTCTGAAGCAGCTTCA 1367 SEQ ID NO: 1857 -7.7 -25.4 75 -15.1 -2 -13.2

CAGCAGTTCTGAAGCAGCTT 1369 SEQ ID NO: 1858 -7.7 -25 73.6 -16.2 -0.8 -9.7

AACTGGAGAGAACGAAGTTT 1552 SEQ ID NO: 1859 -7.7 -19 57.4 -9.5 -1.8 -5.5

AGAGGTATTCTTCAGCCTGC 1776 SEQ ID NO: 1860 -7.7 -25.8 76.7 -17.2 -0.8 -4.5

TGATTCACAGTTTGCAATAC 2067 SEQ ID NO: 1861 -7.7 -19.8 60.8 -12.1 0 -7.1

AGCTGATGCATTCTTGAGAA 2315 SEQ ID NO: 1862 -7.7 -21.8 65.2 -12.5 -1.6 ^• -8.2

AGGTACAGCTGATGCATTCT 2321 SEQ ID NO: 1863 -7.7 -24.2 71.9 -14.9 -1.6 -8.4

TAGAATTTCCTATTAGCTGT 2493 SEQ ID NO: 1864 -7.7 -20.5 62.9 -12.8 0 -4.8

ATTAATTCACACTTACATAA 2604 SEQ ID NO: 1865 -7.7 -16 52 -8.3 0 -3.8

ATGTAAAAATCACCATTTCC 2978 SEQ ID NO: 1866 -7.7 -18.7 56.4 -10.3 -0.4 -2.8

CGCATGTTAATAATACTGAT 3145 SEQ ID NO: 1867 -7.7 -18 55.2 -10.3 0 -5.2

AACAAATGTTGATCCACATC 3221 SEQ ID NO: 1868 -7.7 -19.1 57.7 -10.7 -0.4 -4.4

ATAATTAAGTACTGTTAAAA 3383 SEQ ID NO: 1869 -7.7 -13 45.7 -5.3 0 -6.3

ACTCTGTACTTTTTCCAACA 35 SEQ ID NO: 1870 -7.6 -22.1 66.1 -14.5 0 -4.1

GGGAAGGACACATCAGACTA 137 SEQ ID NO: 1871 -7.6 -22.4 65.8 -14.1 -0.4 -2.9

CCCAGTATCTGAATTAGAAG 248 SEQ ID NO: 1872 -7.6 -20.5 61.2 -12.3 -0.3 -4.1

CCGTGCTTTAAAGACTCTTG 274 SEQ ID NO: 1873 -7.6 -22.3 64.5 -14.2 0 -8.1

CCAGGGCTTCCGTCTCCACT 375 SEQ ID NO: 1874 -7.6 -31.8 85.4 -22.9 -1.2 -4.3

AATTCACCATTTTAAATTGA 450 SEQ ID NO: 1875 -7.6 -16.7 52.8 -9.1 0 -5.4

GTACCTTTTATTATTTTGGA 584 SEQ ID NO: 1876 -7.6 -19.9 61.6 -12.3 0 -3.3

ACATGTGTACCTTTTATTAT 590 SEQ ID NO: 1877 -7.6 -19.9 61.4 -12.3 10 -6.1

AGAGGTAGGCCTTTGGAGGC 898 SEQ ID NO: 1878 -7.6 -27.6 79.9 -16.7 -3.3 -8.7

ACAAAGGGACTTCTGTCATA 946 SEQ ID NO: 1879 -7.6 -21 63.3 -11.3 -2.1 -7.5

GGGCATTGTCATGCTAATGG

974 SEQ ID NO: 1880 -7.6 -24.2 70.1 -13.5 -3.1 -8.9 GGGGCATTGTCATGCTAATG

975 SEQ ID NO: 1881 -7.6 -24.2 70.1 -13.5 -3.1 -8.2 GTGAGGGGGCATTGTCATGC

980 SEQ ID NO: 1882 -7.6 -27.3 79.1 -17.4 -2.3 -6.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TCAGCTTTTCGTGCTTGCTT 1242 SEQ ID NO: 1883 -7.6 -26.1 76.1 -17.7 -0.6 -6

TTAAGAGCTCACTCCAGCAG 1383 SEQ ID NO: 1884 -7.6 -24.2 70.9 -15.1 -1.4 -9.3

GTAGCTGTCCAAATTTCTCT 1722 SEQ ID NO: 1885 -7.6 -23.3 69.6 -15.7 0 -4.8

CCCGTTCAGGTGCTTGTAGT 1796 SEQ ID NO: 1886 -7.6 -28.5 80.7 -20.4 -0.1 -4 :A

TTTAATTAGCGTTACTTGGA 1967 SEQ ID NO: 1887 -7.6 -19.6 59.8 -12 0 -4.1

TATCCATCTGTGAGTTCAAT 2138 SEQ ID NO: 1888 -7.6 -21.6 65.5 -14 0 -3.2

GCTGATGCATTCTTGAGAAT 2314 SEQ ID NO: 1889 -7.6 -21.8 65 -13.2 -0.8 -9.4

TGTGGCTGACACAGGTCCAT 2409 SEQ ID NO: 1890 -7.6 -27 76.9 -17.2 -2.2 -8.4

TTAATAGAATTTCCTATTAG 2497 SEQ ID NO: 1891 -7.6 -15.7 51.7 -6.6 -1.4 -7.1

ATTTTCTTAACATCATGAAC 2565 SEQ ID NO: 1892 -7.6 -16.8 54 -9.2 . 0 -6.9

TTTATGAAATCCAACAATGC 2719 SEQ ID NO: 1893 -7.6 -17.5 53.8 -9.9 0 -3.6

TGTATACTAACAAGACTTCC 2751 SEQ ID NO: 1894 -7.6 -19.1 58.7 -11.5 0 -6.3

AGCAAAATGTGTTTAATGTT 2815 SEQ ID NO: 1895 -7.6 -17.3 54.6 -9.7 0 -5.4

CGTCAATTTTGTTTCCAACT 2863 SEQ ID NO: 1896 -7.6 -21.6 63.3 -13.3 -0.5 -4

TTTGGGGAAGATTTGAATTA 3020 SEQ ID NO: 1897 -7.6 -18.2 56.5 -10.6 0 -3.2

AATAAGGCAAGACTTTCATA 3175 SEQ ID NO: 1898 -7.6 -18 56 -10.4 0 -4

CCCCAGTATCTGAATTAGAA 249 SEQ ID NO: 1899 -7.5 -22.5 64.6 -14.4 -0.3 -4.1

AAACGACAGTAAGGACAACG 652 SEQ ID NO: 1900 -7.5 -18.3 54.4 -10.1 -0.4 -4.2

CCATATGTTTGGTAACCTTG 1009 SEQ ID NO: 1901 -7.5 -22.4 65.2 -14.2 -0.4 -5.8

AGTGGCCATATGTTTGGTAA 1014 SEQ ID NO: 1902 -7.5 -23.4 68.9 -15.1 -0.4 -9

CACACTTCAAAAGTTCCAGT 1158 SEQ ID NO: 1903 -7.5 -21.4 63.3 -13 -0.7 -4.2

TAGCCTGCTCTTGCTGCAAA 1218 SEQ ID NO: 1904 -7.5 -26.3 73.8 -16.5 -2.3 -9.3

CTACCAGCTGGAAGTTTTCA 1635 SEQ ID NO: 1905 -7.5 -23.9 69.8 -14.1 -0.8 -12.7

GTGCTTGTAGTAGAGGTATT 1787 SEQ ID NO: 1906 -7.5 -22.6 70.6 -15.1 0 -3.6

AGTATTTGATTATTATGCCT 2016 SEQ ID NO: 1907 -7.5 -20 61.6 -12.5 0 -3

AGTTCAATCCACTCCATTAC 2126 SEQ ID NO: 1908 -7.5 -23 67.7 -15.5 0 -2.3

TTCTTCATAGTGGAGATCAG 2207 SEQ ID NO: 1909 -7.5 -21 65.7 -12.6 -0.8 -5.5

CTTTACCATGGAGGAATCCT 2281 SEQ ID NO: 1910 -7.5 -23.9 68.1 -13.6 -2.8 -8.5

AGAATTGTTTCAGTTCAGCT 2299 SEQ ID NO: 1911 -7.5 -21.6 66.8 -12.5 -1.5 -6.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo ACAGCTGATGCATTCTTGAG 2317 SEQ ID NO: 1912 -7.5 -22.8 68 -13.7 -1.6 -9.1

CTTCAAAGGAAGAGGGAGGG 2349 SEQ ID NO: 1913 -7.5 -21.8 64 -12.7 -1.5 -4.9

TGGCTGACACAGGTCCATTA 2407 SEQ ID NO: 1914 -7.5 -25.6 73.4 -17.2 -0.7 -8.4

CCTATTAGCTGTTTGCAGGT

2485 SEQ ID NO: 1915 -7.5 -25.4 74.5 -16.1 -1.8 -7.1 TCCTATTAGCTGTTTGCAGG

2486 SEQ ID NO: 1916 -7.5 -24.6 72.7 -15.3 -1.8 -7.1 ATATTAATAGAATTTCCTAT

2500 SEQ ID NO: 1917 -7.5 -15.6 51.3 -8.1 0 -5.9

AAATGGCAAGCTAACATATT 2515 SEQ ID NO: 1918 -7.5 -18 55.1 -10.5 0 -5.5

TTAAATGGCAAGCTAACATA 2517 SEQ ID NO: 1919 -7.5 -17.7 54.6 -10.2 0 -5.5

CCCTCAGAACATATTTAAAT 2531 SEQ ID NO: 1920 -7.5 -19 56.9 -11.5 0 -6

TCCAACAATGCCAAAGCCAC 2710 SEQ ID NO: 1921 -7.5 -24.4 66 -16 -0.7 -3.2

GCATGTTAATAATACTGATA 3144 SEQ ID NO: 1922 -7.5 -16.9 53.9 -9.4 0 -5.2

CAAATGTTGATCCACATCTG 3219 SEQ ID NO: 1923 -7.5 -20.5 60.8 -12.2 -0.6 -4.9

GACATAGAATAATTAAGTAC 3391 SEQ ID NO: 1924 -7.5 -14.3 48.5 -6.8 0 -4.5

GGAGCCCATAATGGTACCCA 525 SEQ ID NO: 1925 -7.4 -28.3 75.5 -20.2 -0.4 -7.8

TGTTTTGAATTGCAGAGGAA 870 SEQ ID NO: 1926 -7.4 -19.7 60 -12.3 0 -5.3

TATGGACTCGGGTGAGCTGG 1076 SEQ ID NO: 1927 -7.4 -25.9 73.6 -17.1 -1.3 -5.6

ACACTTCAAAAGTTCCAGTA 1157 SEQ ID NO: 1928 -7.4 -20.4 61.6 -12.1 -0.7 -4.2

CTTGCTTCGGTTAGCCTGCT 1229 SEQ ID NO: 1929 -7.4 -28.6 80.2 -20.3 -0.7 -5.2

CAGCTTTTCGTGCTTGCTTC 1241 SEQ ID NO: 1930 -7.4 -26.1 76.1 -17.9 -0.6 -6

GCCCAGTAACCAGGAAGATG 1449 SEQ ID NO: 1931 -7.4 -25.3 69.8 -17.9 0 -4

TCAAACTGGAGAGAACGAAG 1555 SEQ ID NO: 1932 -7.4 -18 54.7 -10.6 0 -3.5

GCTGGAAGTTTTCAAGGTTT 1629 SEQ ID NO: 1933 -7.4 -22.3 67.2 -14 -0.8 -4.6

AGTAGCTGTCCAAATTTCTC 1723 SEQ ID NO: 1934 -7.4 -22.4 67.8 -15 0 -4.8

AGCTCCTAGGGGTTGTAACT 1869 SEQ ID NO: 1935 -7.4 -25.9 75.6 -17.8 -0.2 -8.6

AGCAGAGCTCCTAGGGGTTG 1874 SEQ ID NO: 1936 -7.4 -27.7 80.4 -19.4 -0.4 -9.1

CTAATTAATAAGATTAGTTC 2233 SEQ ID NO: 1937 -7.4 -14.1 48.5 -5.8 -0.8 -4.7

TCTAAGTTGCTTTAGCTATG 2663 SEQ ID NO: 1938 -7.4 -20.6 63.9 -11.8 -1.3 -6.5

TTATGAAATCCAACAATGCC 2718 SEQ ID NO: 1939 -7.4 -19.4 57 -12 0 -3

TATTTGACATCCTAGCAAAA 2828 SEQ ID NO: 1940 -7.4 -18.8 57.1 -10.5 -0.7 -4.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GAACTGTGACTATTTGACAT 2838 SEQ ID NO: 1941 -7.4 -19.3 59.3 -11.9 0 -3.3

TTCCTTTCTCTTTGCATAGA 2891 SEQ ID NO: 1942 - 1 . i -23.2 70.1 -15.8 0 -3.4

AGGACACATCAGACTACAGT 133 SEQ ID NO: 1943 -7.3 -22.2 66.8 -14.2 -0.4 -3.9

CAGCTTGTCAAATTTCGTGG 161 SEQ ID NO: 1944 -7.3 -22.2 65.1 -14.9 0 -4:5

CACCAATAGGTGTAAGTCCG 291 SEQ ID NO: 1945 -7.3 -23.6 66.8 -13.7 -2.6 -7.4

GCGACCGCGGGCGGGGATGG 338 SEQ ID NO: 1946 -7.3 -33.2 81 -23.6 -1.9 -12.4

ATGGTCAGGTCAGAGGGCAT 850 SEQ ID NO: 1947 -7.3 -26.5 78.2 -19.2 0 -4

GGGGGCATTGTCATGCTAAT 976 SEQ ID NO: 1948 -7.3 -25.4 72.8 -15 -3.1 -7.1

CTGGCTCACACTTCAAAAGT 1164 SEQ ID NO: 1949 -7.3 -22.2 65.1 -14.2 -0.5 -4.7

AGCAGCTTCATTTGGTCATC 1357 SEQ ID NO: 1950 -7.3 -24.5 74.1 -17.2 . 0 -5.6

TAACCAGGAAGATGGATCCT 1443 SEQ ID NO: 1951 -7.3 -22.7 64.9 -14.1 -1.2 -8.5

TTTGCAATACAAATACCCTG 2057 SEQ ID NO: 1952 -7.3 -20 58.4 -11.4 -1.2 -7.1

CTGGGGCTGTGAAGCTTTGA 2084 SEQ ID NO: 1953 -7.3 -25.8 73.9 -16 -2.5 -8.9

AGGGGCTATTGTAGGTACAG 2333 SEQ ID NO: 1954 -7.3 -24 72 -16.7 0 -5.2

CCTTAATATTAATTCACACT 2611 SEQ ID NO: 1955 -7.3 -18 55.8 -10.7 0 -7.3

TATACTAACAAGACTTCCTG 2749 SEQ ID NO: 1956 -7.3 -18.8 57.7 -11.5 0 -2.8

AAAAATCACCATTTCCATCC 2974 SEQ ID NO: 1957 -7.3 -20.9 60.1 -12.9 -0.4 -2.8

CAGTATCACTCTCTTCCTTT 3044 SEQ ID NO: 1958 -7.3 -24 72.7 -16.7 0 -2.5

GAAATAAGGCAAGACTTTCA 3177 SEQ ID NO: 1959 -7.3 -18.2 56 -10.4 -0.2 -4.9

AAATCCCCAGTATCTGAATT 253 SEQ ID NO: 1960 -7.2 -21.9 63 -14.1 -0.3 -4.1

GCCCTGTTCCCCATGCGATC 404 SEQ ID NO: 1961 -7.2 -32.7 84.5 -25.5 0 -4.2

TTAAGTCCATTGGCTCGGAT 799 SEQ ID NO: 1962 -7.2 -24.4 69.7 -17.2 0.1 -6.6

GAGGTAGGCCTTTGGAGGCA 897 SEQ ID NO: 1963 -7.2 -28.3 80.6 -16.7 -4.4 -9.9

TATGTTTGGTAACCTTGCAG 1006 SEQ ID NO: 1964 -7.2 -22.2 65.9 -14.3 -0.4 -5.7

TGGACTCGGGTGAGCTGGTA 1074 SEQ ID NO: 1965 -7.2 -27.1 77.1 -18.5 -1.3 -5.6

ATTAAGAGCTCACTCCAGCA 1384 SEQ ID NO: 1966 -7.2 -24.2 70.6 -15.5 -1.4 -8.5

GAGTTCAATCCACTCCATTA 2127 SEQ ID NO: 1967 -7.2 -23.4 68.4 -15.5 -0.5 -3.8

AAGCTCAAATCCCCCGCTGT■ 2259 SEQ ID NO: 1968 -7.2 -28.8 75 -21 -0.3 -5

AACATATTTAAATGGCAAGC 2524 SEQ ID NO: 1969 -7.2 -17.2 53.6 -9.5 -0.1 -6.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GCATTTGCTTTGAAAGTTTG 2641 SEQ ID NO: 1970 -7.2 -20.2 61.4 -13 0 -6.1

TAAGTTGCTTTAGCTATGGA 2661 SEQ ID NO: 1971 -7.2 -21.1 64.4 -12.5 -1.3 -6.5

GCCAAAGCCACATTTCAGCA 2701 SEQ ID NO: 1972 -7.2 -26.3 72.2 -18.3 -0.6 -4.1

TAGCAAAATGTGTTTAATGT 2816 SEQ ID NO: 1973 -7.2 -16.9 53.8 -9.7 0 -5.4

ATGTTAATAATACTGATAAT 3142 SEQ ID NO: 1974 -7.2 -13.7 47.1 -6.5 0 -3.2

AAATAAGGCAAGACTTTCAT 3176 SEQ ID NO: 1975 -7.2 -17.6 54.8 -10.4 0 -4

AAATTGTGAAATAAGGCAAG 3184 SEQ ID NO: 1976 -7.2 -15.1 49.1 -7 -0.8 -5.5

ATTTTAAACAAATGTTGATC 3227 SEQ ID NO: 1977 -7.2 -14.4 48.5 -6.5 -0.4 -6.4

AGTACTGTTAAAAATAATTA 3376 SEQ ID NO: 1978 -7.2 -13 45.7 -5.8 0 -5.5

ATTAAGTACTGTTAAAAATA 3380 SEQ ID NO: 1979 -7.2 -1.3 45.7 -5.8 0 -6.3

AATCCAGAATTCATAAAGTT 75 SEQ ID NO: 1980 -7.1 -17.1 53.9 -10 0 -7.4

GCTTGTCAAATTTCGTGGCC 159 SEQ ID NO: 1981 -7.1 -25.3 71.5 -18.2 0 -6.2

AATTAGAAGACATTCTTAGT 237 SEQ ID NO: 1982 -7.1 -16.9 54.8 -8.4 -1.3 -6.2

GCCAGTCCCAGGGCTTCCGT 382 SEQ ID NO: 1983 -7.1 -34.4 90.8 -25.7 -1.5 -7.2

CATGTTTTCCGGCATCTGGC 422 SEQ ID NO: 1984 -7.1 -27.4 76.6 -19.6 -0.5 -6.3

GCCCATAATGGTACCCAGAC 522 SEQ ID NO: 1985 -7.1 -27.3 73.6 -19.3 -0.7 -7.8

TACCTTTTATTATTTTGGAC 583 SEQ ID NO: 1986 -7.1 -18.9 59 -11.8 0 -3.3

CGGCCCTTACAGCTTCTAGC 699 SEQ ID NO: 1987 -7.1 -29 79.6 -20.9 -0.9 -8

TGTACATTGGCCCAAACTTA 741 SEQ ID NO: 1988 -7.1 -23.1 65.5 -16 0 -6.6

CTCTTGTACATTGGCCCAAA 745 SEQ ID NO: 1989 -7.1 -24.5 68.8 -17.4 0 -6.6

GTCCATTGGCTCGGATGAGG 795 SEQ ID NO: 1990 -7.1 -27.1 76 -18.6 -1.3 -7.8

ACTTGATGGCCCGGCTAGGA 1035 SEQ ID NO: 1991 -7.1 -29 77.8 -21.2 -0.4 -8.1

CCATATATGAATAGCCCATT 1095 SEQ ID NO: 1992 -7.1 -22.3 63.5 -14.7 0 -7.5

ATGGAGAAGAGAGTTTGATC 1291 SEQ ID NO: 1993 -7.1 -19.3 60.6 -12.2 10 -4.2

CTCGACAATGGAGAAGAGAG 1298 SEQ ID NO: 1994 -7.1 -19.8 59.2 -12.7 0 ^■ -4.4

AAACTGGAGAGAACGAAGTT 1553 SEQ ID NO: 1995 -7.1 -18.2 55.3 -9.5 -1.6 -5.5

GAAGAAGTAGCTGTCCAAAT 1728 SEQ ID NO: 1996 -7.1 -20.3 60.7 -13.2 0 -4.8

TAGAGGTATTCTTCAGCCTG 1777 SEQ ID NO: 1997 -7.1 -23.7 71.4 -15.7 -0.8 -4.5

GGCATGCAACATTTCAATGA 1838 SEQ ID NO: 1998 -7.1 -21.6 63 -13.3 -0.3 -10.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CCCCACTCCCCCAATCTCTT 1905 SEQ ID NO: 1999 -7.1 -32.9 83.4 -25.8 0 -1.1

ATTGTAGGTACAGCTGATGC 2326 SEQ ID NO: 2000 -7.1 -23.1 69.7 -15.1 -0.5 -9.1

TACAGATTCGGTGACCACAG 2386 SEQ ID NO: 2001 -7.1 -23.3 67 -16.2 0 -6.1

ACATCATGAACACGAGACAA 2556 SEQ ID NO: 2002 -7.1 -19.2 57.1 -12.1 0 -β: 9

CTTAACATCATGAACACGAG 2560 SEQ ID NO: 2003 -7.1 -18.4 55.8 -11.3 0 -6.9

TCAGCAACAGTAGCAGAAAT 2687 SEQ ID NO: 2004 -7.1 -20.4 61.3 -12.3 -0.9 -4.5

ATCCTTTCCTTTCTCTTTGC 2896 SEQ ID NO: 2005 -7.1 -25.6 75.9 -18.5 0 -2.6

TTGAATTACTTTAATATCTT

3008 SEQ ID NO: 2006 -7.1 -15.2 50.8 -8.1 0 -3.2 TTTGAATTACTTTAATATCT

3009 SEQ ID NO: 2007 -7.1 -15.2 50.8 -8.1 0 -3.2 CTTTTAAAATTGTGAAATAA

3190 SEQ ID NO: 2008 -7.1 -12.3 44 -4.3 -0.8 -6.7

GTTGATCCACATCTGCACAG 3214 SEQ ID NO: 2009 -7.1 -24.6 71.5 -16.8 -0.5 -5.3

ACACTATATCTTATTTGACT 3265 SEQ ID NO: 2010 -7.1 -18.4 58.3 -11.3 0 -2.4

TTTTTCCAACATTAGTGACC 26 SEQ ID NO: 2011 -7 -21.5 63.8 -14.5 0 -3.3

ATTGAGCAAAAGAAAAGTGC 180 SEQ ID NO: 2012 -7 -16.6 52.2 -9.6 0.1 -4.3

AGCCAGTCCCAGGGCTTCCG 383 SEQ ID NO: 2013 -7 -33.2 87.5 -23.9 -2.3 -7.6

CCCATGCGATCGAGCCAGTC 395 SEQ ID NO: 2014 -7 -29.8 78.5 -22.3 0.6 -8.8

TCTCCACACACGGGACAAAG 496 SEQ ID NO: 2015 -7 -23.7 66 -16.2 -0.2 -4.2

ACCTGAGACATGGCTTCTAG 820 SEQ ID NO: 2016 -7 -24.2 70.6 -17.2 0 -5.2

TGGAGGCAGAGTGGATGTTT

885 SEQ ID NO: 2017 -7 -24.5 72.7 -17.5 0 -3.2 TTGGAGGCAGAGTGGATGTT

886 SEQ ID NO: 2018 -7 -24.5 72.7 -17.5 0 -4 TTTGGAGGCAGAGTGGATGT

887 SEQ ID NO: 2019 -7 -24.5 72.7 -17.5 0 -4 TCTGGCTCACACTTCAAAAG

1165 SEQ ID NO: 2020 -7 -21.4 63.5 -14.4 0 -3.7

GCCTGGACTTGAGGCTCATC 1183 SEQ ID NO: 2021 -7 -27.7 79.2 -18.4 -2.3 -7.2

TTTTAGCCTGGACTTGAGGC 1188 SEQ ID NO: 2022 -7 -25.3 73.4 -16.7 -1.5 -6.4

AGGCCATGATTTTAGCCTGG 1197 SEQ ID NO: 2023 -7 -26.2 73.8 -17.2 -2 -7.7

TCGGTTAGCCTGCTCTTGCT 1223 SEQ ID NO: 2024 -7 -28.9 81.6 -19.9 -2 -7.1

AAGCAGCTTCATTTGGTCAT 1358 SEQ ID NO: 2025 -7 -23.4 69.8 -15.9 0 -7.5

AGTCGAAGAAGTAGCTGTCC 1732 SEQ ID NO: 2026 -7 -23.4 69.1 -15.6 -0.6 -5.8

ATCCCCGTTCAGGTGCTTGT 1799 SEQ ID NO: 2027 -7 -30 82.6 -22.5 -0.1 -4.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TGAAAGCAGAGCTCCTAGGG 1878 SEQ ID NO: 2028 -7 -24.4 70.1 -16.5 -0. 8 -8.8

AATCCACTCCATTACAATGT 2121 SEQ ID NO: 2029 -7 -21.8 63.4 -14.8 0 -5.1

CTGACCGTGTTGGTATCCAT 2151 SEQ ID NO: 2030 -7 -26.2 73.4 -17.6 -1. 5 -5.1

CTAACATATTAATAGAATTT 2505 SEQ ID NO: 2031 -7 -13.4 46.5 -6.4 0 -5.9

TTTAAATGGCAAGCTAACAT 2518 SEQ ID NO: 2032 -7 -18.1 55.4' -11.1 0 -4.8

GCCTGCATTTTCTTAACATC 2571 SEQ ID NO: 2033 -7 -23.2 68.2 -16.2 0 -4.9

TATGAAATCCAACAATGCCA 2717 SEQ ID NO: 2034 -7 -20 57.9 -13 0 -3

GCAAAATGTGTTTAATGTTG 2814 SEQ ID NO: 2035 -7 -17.3 54.5 -10.3 0 -5.4

TTGCTATTTTGTTATATCAC 3320 SEQ ID NO: 2036 -7 -18.8 59.7 -11.8 0 -3.6

AGCTTGTCAAATTTCGTGGC 160 SEQ ID NO: 2037 -6.9 -23.3 68.1 -16.4 0 -4.5

TCATTGAGCAAAAGAAAAGT 182 SEQ ID NO: 2038 -6.9 -15.9 50.9 -9 0 -4.3

AGCCCATAATGGTACCCAGA 523 SEQ ID NO: 2039 -6.9 -27.1 73.3 -19.3 -0. 7 -7.8

CTTACAGCTTCTAGCTTCAT 694 SEQ ID NO: 2040 -6.9 -23.3 70.6 -14.8 -1. 6 -5.8

AAACTTATTCCTTCCTCCAC 728 SEQ ID NO: 2041 -6.9 -23.6 67.6 -16.7 0 -1.3

GGTAACCTTGCAGGCTGCCG 999 SEQ ID NO: 2042 -6.9 -29.6 78.9 -21.1 -1. 4 -10.1

TACTACTCCTGGCCCACTCG 1314 SEQ ID NO: 2043 -6.9 -28.9 77.7 -22 0 -6.6

CACTTGTCGGTAAATGTGGT 1409 SEQ ID NO: 2044 -6.9 -22.6 66.1 -15.7 0 -3.8

CCACTCCCCCAATCTCTTTT 1903 SEQ ID NO: 2045 -6.9 -29.1 77.8 -22.2 0 -1.1

AAGCTTTGATTCACAGTTTG 2073 SEQ ID NO: 2046 -6.9 -20.3 62.5 -13.4 0 -6.5

TGAGTTCAATCCACTCCATT

2128 SEQ ID NO: 2047 -6.9 -23.7 68.9 -15.5 -1. 2 -4.6 GTGAGTTCAATCCACTCCAT

2129 SEQ ID NO: 2048 -6.9 -24.8 71.9 -16.6 -1. 2 -4.6 GCTGACACAGGTCCATTAGT

2405 SEQ ID NO: 2049 -6.9 -25.6 74.7 -17.3 -1. 3 -5.4

CTAGCAAAATGTGTTTAATG 2817 SEQ ID NO: 2050 -6.9 -16.6 52.9 -9.7 0 -5.4

TGACTATTTGACATCCTAGC 2832 SEQ ID NO: 2051 -6.9 -21.9 65.5 -15 io -3.5

AATTGCAGCAAGAATGAACC 2936 SEQ ID NO: 2052 -6.9 -19.7 58 -12.1 0 -8.8

ATCACTCTCTTCCTTTCCCC 3040 SEQ ID NO: 2053 -6.9 -28.8 81.3 -21.9 0 -0.3

TGTGGCATCGCATGTTAATA 3153 SEQ ID NO: 2054 -6.9 -22.6 65.8 -14.8 -0. 7 -5.2

AAGACTTTCATACCTGTGGC 3167 SEQ ID NO: 2055 -6.9 -23.3 68.4 -16.4 0 -3.3

TAAAATTGTGAAATAAGGCA 3186 SEQ ID NO: 2056 -6.9 -14.8 48.5 -7 -0. 8 -4.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AGTATTAATACTTTATTTTA 3241 SEQ ID NO: 2057 -6.9 -14.7 50.3 -6.5 -0.2 -10.5

AGAAATCATTGAGCAAAAGA 187 SEQ ID NO: 2058 -6.8 -16 51.1 -9.2 0 -4.3

CCAGTATCTGAATTAGAAGA 247 SEQ ID NO: 2059 -6.8 -19.1 58.7 -11.7 -0.3 -4.1

AGTCCGTGCTTTAAAGACTC 277 SEQ ID NO: 2060 -6.8 -22.9 67.2 -15.3 -0.6 -i :ι

GGCCCTGTTCCCCATGCGAT 405 SEQ ID NO: 2061 -6.8 -33.5 85.2 -25.8 -0.7 -5.6

TGTACCTTTTATTATTTTGG 585 SEQ ID NO: 2062 -6.8 -19.3 60.1 -12.5 0 -4.2

TTTTTGAAAACGACAGTAAG 659 SEQ ID NO: 2063 -6.8 -15.6 50.3 -8.8 0 -4.3

TCAGGGCCCTGTCTCTCTTG 759 SEQ ID NO: 2064 -6.8 -29.4 84.4 -18.8 -0.3 -15.8

^■ CGTGCTTGCTTCGGTTAGCC 1233 SEQ ID NO: 2065 -6.8 -28.8 79.4 -21.1 -0.7 -5.6

TGCTTGTAGTAGAGGTATTC 1786 SEQ ID NO: 2066 -6.8 -21.8 68.7 -15 0 -3.6

CCCCGTTCAGGTGCTTGTAG 1797 SEQ ID NO: 2067 -6.8 -29.3 80.6 -22 -0.1 -4.4

GGGTTGTAACTTATGCTCTT 1860 SEQ ID NO: 2068 -6.8 -22.9 69 -16.1 0 -4.3

CCTGATACATCATTTATTTG 2041 SEQ ID NO: 2069 -6.8 -19.3 59.2 -12.5 0 -5

GCTTTAGCTATGGAGCATTT 2655 SEQ ID NO: 2070 -6.8 -23.5 70.1 -14.2 -2.5 -9

AATCCAACAATGCCAAAGCC 2712 SEQ ID NO: 2071 -6.8 -22.8 62.6 -15.1 -0.7 -3.2

AAAAAGACTGATGTATACTA 2762 SEQ ID NO: 2072 -6.8 -14.9 49.4 -8.1 0 -6.3

CATGTAAAAATCACCATTTC 2979 SEQ ID NO: 2073 -6.8 -17.4 54 -9.9 -0.4 -4.1

GAATTACTTTAATATCTTTC 3006 SEQ ID NO: 2074 -6.8 -15.6 52 -8.8 0 -3.2

CACATCTGCACAGCTACCTT 3207 SEQ ID NO: 2075 -6.8 -25.9 73.5 -18.5 -0.3 -4.8

AAGTACTGTTAAAAATAATT 3377 SEQ ID NO: 2076 -6.8 -12.6 44.7 -5.8 0 -6.3

CATTGAGCAAAAGAAAAGTG 181 SEQ ID NO: 2077 -6.7 -15.5 49.8 -8.8 0 -4.3

AGAAGACATTCTTAGTGAAA 233 SEQ ID NO: 2078 -6.7 -17 54.4 -9.1 -1.1 -4.6

CATTTTAAATTGAGACACTT 443 SEQ ID NO: 2079 -6.7 -16.7 53.3 -10 0 -4.6

TAATTCACCATTTTAAATTG 451 SEQ ID NO: 2080 -6.7 -15.8 51 -9.1 0 -4.8

TCGGCCCTTACAGCTTCTAG 700 SEQ ID NO: 2081 -6.7 -27.6 77 -20.2 -0.4 -6.2

TTGGATCACCTGAGACATGG 827 SEQ ID NO: 2082 -6.7 -23.4 67.7 -15.7 -0.9 -6.4

TTTTGAATTGCAGAGGAAAT 868 SEQ ID NO: 2083 -6.7 -17.8 55.3 -11.1 0 -5.2

CTTTGGAGGCAGAGTGGATG• 888 SEQ ID NO: 2084 -6.7 -24.2 71.2 -17.5 0 -4

TGGGTACTCAGACTTGATGG 1046 SEQ ID NO: 2085 -6.7 -23.1 68.8 -15.8 -0.3 -6.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AGCTCGTCTGGTAACTATCC 1113 SEQ ID NO: 2086 -6.7 -25 72.8 -18.3 0 -4.3

ATCTAAACTAAAGAGCACCA

1604 SEQ ID NO: 2087 -6.7 -19 57.2 -12.3 0 -4.1 CATCTAAACTAAAGAGCACC

1605 SEQ ID NO: 2088 -6.7 -19 57.2 -12.3 0 -4.1 TAGGGGTTGTAACTTATGCT

1863 SEQ ID NO: 2089 -6.7 -22.4 67.3 -15.7 0 -3.6 CTAGGGGTTGTAACTTATGC

1864 SEQ ID NO: 2090 -6.7 -22.4 67.3 -15.7 0 -4.3 CATTTATTTGCTATTAGTAT

2031 SEQ ID NO: 2091 -6.7 -17.9 57.4 -11.2 0 -3.6

GGCTGTTCATGATTTGGTGG 2442 SEQ ID NO: 2092 -6.7 -24.7 73 -18 0 -6.4

TGCTTTAGCTATGGAGCATT

2656 SEQ ID NO: 2093 -6.7 -23.4 69.6 -14.2 -2.5 -10.3 TTGCTTTAGCTATGGAGCAT

2657 SEQ ID NO: 2094 -6.7 -23.4 69.6 -14.2 -2.5 -10.7 AAGACTGATGTATACTAACA

2759 SEQ ID NO: 2095 -6.7 -17.2 54.6 -10.5 0 -6.3

CCATATTTGTTCTACAGCAG 3089 SEQ ID NO: 2096 -6.7 -22.3 66.7 -15.6 0 -4.1

TTTGCGATTCTTTGTCCTCC 3108 SEQ ID NO: 2097 -6.7 -25.9 74.2 -19.2 0 -4.1

ATTAATACTTTATTTTAAAC 3238 SEQ ID NO: 2098 -6.7 -12.6 45.1 -5.9 0 -4.4

TCAGGACCTAAAGAATGTAA 3285 SEQ ID NO: 2099 -6.7 -18.4 56.2 -11.7 0 -3.8

GAGGGCATAGCTTGGATCAC 838 SEQ ID NO: 2100 -6.6 -25.1 73.3 -17.8 -0.4 -5.7

AATGGTCAGGTCAGAGGGCA 851 SEQ ID NO: 2101 -6.6 -25.8 75.5 -19.2 0 -4

TTTGAATTGCAGAGGAAATG 867 SEQ ID NO: 2102 -6.6 -17.7 54.9 -11.1 0 -5.2

CTGCAAATAGGCCATGATTT 1205 SEQ ID NO: 2103 -6.6 -22.2 63.9 -15.1 0 -7.7

CGGTTAGCCTGCTCTTGCTG 1222 SEQ ID NO: 2104 -6.6 -28.5 79.6 -19.9 -2 -7.1

GCTTCATTTGGTCATCAACC 1353 SEQ ID NO: 2105 -6.6 -24.2 70.9 -16.6 -0.9 -4.6

CTGGAGAGAACGAAGTTTTG 1550 SEQ ID NO: 2106 -6.6 -19.6 59 -11.2 -1.8 -6.3

TCCTGGACACCTTCTACCAG 1648 SEQ ID NO: 2107 -6.6 -27.1 75.5 -18.8 -1.7 -6

CAAATTTCTCTGTCTGCTGC 1713 SEQ ID NO: 2108 -6.6 -23.1 68.8 -16.5 0 -5

AGAAGTAGCTGTCCAAATTT

1726 SEQ ID NO: 2109 -6.6 -20.6 62.1 -14 10 -4.8 AAGAAGTAGCTGTCCAAATT

1727 SEQ ID NO: 2110 -6.6 -19.8 59.8 -13.2 0 -4.8 TATAGGGCACATCCCCGTTC

1809 SEQ ID NO: 2111 -6.6 -28.1 76.7 -19.5 -2 -6.9

TCCTAGGGGTTGTAACTTAT 1866 SEQ ID NO: 2112 -6.6 -23 68.5 -15.7 -0.2 -8.6

TCTTCATAGTGGAGATCAGT 2206 SEQ ID NO: 2113 -6.6 -22.1 68.8 -14.8 -0.5 -5.5

AATGGCAAGCTAACATATTA 2514 SEQ ID NO: 2114 -6.6 -18.4 56.3 -11.8 0 -5.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CTGCCAGAAATTTTTTATGA 2732 SEQ ID NO: 2115 -6.6 -19.4 58.6 -12 -0.6 -5.3

ATTTGACATCCTAGCAAAAT 2827 SEQ ID NO: 2116 -6.6 -19.1 57.6 -11.6 -0.7 -4.6

CCTTTCTCTTTGCATAGATT 2889 SEQ ID NO: 2117 -6.6 -22.8 68.4 -16.2 0 -3.7

TTCTACAGCAGACTTTGGTC 3080 SEQ ID NO: 2118 -6.6 -23.2 70.7 -15.1 -1.4 -6'.7

ACAAATGTTGATCCACATCT 3220 SEQ ID NO: 2119 -6.6 -20.7 61.5 -13.3 ^' -0.6 -4.9

AAACAAATGTTGATCCACAT 3222 SEQ ID NO: 2120 -6.6 -18 54.7 -10.7 -0.4 -4.7

AAATTACCGCTTTTGCTATT 3332 SEQ ID NO: 2121 -6.6 -20.9 61 -12.7 -1.5 -5.5

TTTCCCTGGACTCTGTACTT 44 SEQ ID NO: 2122 -6.5 -25.8 74.8 -19.3 0 -4.8

CCTGTTCCCCATGCGATCGA 402 SEQ ID NO: 2123 -6.5 -30.3 78.1 -23.1 0 -8.8

CATCTGGCCCTGTTCCCCAT 410 SEQ ID NO: 2124 -6.5 -32.3 84.9 -25.8 0 -5.9

TCCATTGGCTCGGATGAGGG 794 SEQ ID NO: 2125 -6.5 -27.1 75.1 -19.2 -1.3 -7.8

ATGGACTCGGGTGAGCTGGT 1075 SEQ ID NO: 2126 -6.5 -27.4 77.7 -19.7 -1.1 -5.6

TTTTGCACATAAGCCCAAAG 1266 SEQ ID NO: 2127 -6.5 -21.8 62.3 -14.8 -0.2 -5

ACTCGACAATGGAGAAGAGA 1299 SEQ ID NO: 2128 -6.5 -20 59.5 -12.7 -0.6 -5.1

CCCACTCCCCCAATCTCTTT 1904 SEQ ID NO: 2129 -6.5 -31 80.6 -24.5 0 -1.1

AGTTTGCAATACAAATACCC 2059 SEQ ID NO: 2130 -6.5 -20.3 59.7 -12.1 -1.7 -8.1

GAGAATTGTTTCAGTTCAGC 2300 SEQ ID NO: 2131 -6.5 -21.3 66.2 -13.2 -1.5 -5.8

TAGGTACAGCTGATGCATTC 2322 SEQ ID NO: 2132 -6.5 -23 69.2 -14.9 -1.6 -9.1

GCTATTGTAGGTACAGCTGA 2329 SEQ ID NO: 2133 -6.5 -23.7 71.3 -16.4 -0.2 -9.1

TAACATATTAATAGAATTTC 2504 SEQ ID NO: 2134 -6.5 -12.9 45.7 -6.4 0 -5.4

TGCCAGAAATTTTTTATGAA 2731 SEQ ID NO: 2135 -6.5 -17.8 54.9 -10.5 -0.6 -5.4

AATGTGTTTAATGTTGTATT 2810 SEQ ID NO: 2136 -6.5 -17.2 55.6 -10.7 0 -2.5

GGGGAAGATTTGAATTACTT 3017 SEQ ID NO: 2137 -6.5 -19.2 58.7 -12.7 0 -3.2

TCTTTGTCCTCCCATATTTG 3100 SEQ ID NO: 2138 -6.5 -25 72.4 -18.5 0 -2.1

TCGCATGTTAATAATACTGA 3146 SEQ ID NO: 2139 -6.5 -18.4 56.4 -11.9 0 -5.2

AAAATTGTGAAATAAGGCAA 3185 SEQ ID NO: 2140 -6.5 -14.4 47.6 -7 -0.8 -5.5

CTAAAGAATGTAAACACTAT 3278 SEQ ID NO: 2141 -6.5 -14.3 47.9 -7.8 0 -4.2

AATTACCGCTTTTGCTATTT 3331 SEQ ID NO: 2142 -6.5 -21.7 63.3 -13.-6 -1.5 -5.2

CTGTTAAAAATAATTACCAA 3372 SEQ ID NO: 2143 -6.5 -14.1 47.1 -7.6 0 -4.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TTAAGTACTGTTAAAAATAA 3379 SEQ ID NO: 2144 -6.5 -12.3 44.2 -5.8 0 -6.3

TCCAACATTAGTGACCTGCT 22 SEQ ID NO: 2145 -6.4 -24.7 70.3 -18.3 0 -3.6

CAGAATTCATAAAGTTACAA 71 SEQ ID NO: 2146 -6.4 -15.3 50.2 -8.9 0 -7.4

ATCAGACTACAGTAACCCTT 126 SEQ ID NO: 2147 -6.4 -22.8 66.6 -16.4 0 -3.2

CATTCTTAGTGAAATTATAG 227 SEQ ID NO: 2148 -6.4 -15.8 52.2 -8.7 -0.4 -3.5

ATGTTTTGAATTGCAGAGGA 871 SEQ ID NO: 2149 -6.4 -20.4 62.1 -14 0 -5.3

GCTGCCGTGAGGGGGCATTG 986 SEQ ID NO: 2150 -6.4 -30.5 82.2 -21.5 -2.6 -8.2

GCCCATTATGGACTCGGGTG 1082 SEQ ID NO: 2151 -6.4 -28 76.2 -20.6 -0.9 -6.8

ATTTTAGCCTGGACTTGAGG 1189 SEQ ID NO: 2152 -6.4 -23.5 69 -17.1 0 -4.5

GGTCGAGGATTAAGAGCTCA 1392 SEQ ID NO: 2153 -6.4 -23.5 69 -16 -0.9 -9.3

AACCAGGAAGATGGATCCTT 1442 SEQ ID NO: 2154 -6.4 -23.1 65.8 -15.3 -1.3 -8.5

AGTAACCAGGAAGATGGATC 1445 SEQ ID NO: 2155 -6.4 -21 62.7 -14.1 -0.1 -4.1

CCAGCTGGAAGTTTTCAAGG 1632 SEQ ID NO: 2156 -6.4 -23.6 68.4 -15.6 -0.8 -11.2

CACTCCCCCAATCTCTTTTT 1902 SEQ ID NO: 2157 -6.4 -27.2 74.8 -20.8 0 -1.1

TACAGCTGATGCATTCTTGA 2318 SEQ ID NO: 2158 -6.4 -22.5 67.1 -14.5 -1.6 -9.1

TTTCCTATTAGCTGTTTGCA 2488 SEQ ID NO: 2159 -6.4 -23.6 70.5 -15.6 -1.5 -4.8

AAGTTTGTAGTCATTTCCCT 2628 SEQ ID NO: 2160 -6.4 -23.4 70.2 -17 0 -2

AAGTTGCTTTAGCTATGGAG 2660 SEQ ID NO: 2161 -6.4 -21.4 65.2 -14.2 -0.6 -5.9

TGCCAAAGCCACATTTCAGC 2702 SEQ ID NO: 2162 -6.4 -25.6 71 -18.3 -0.7 -3.9

GCCAGAAATTTTTTATGAAA 2730 SEQ ID NO: 2163 -6.4 -17.1 53.3 -9.9 -0.6 -5.4

TGGGGAAGATTTGAATTACT 3018 SEQ ID NO: 2164 -6.4 -19.1 58.3 -12.7 0 -3.2

GCATCGCATGTTAATAATAC 3149 SEQ ID NO: 2165 -6.4 -19.4 58.5 -13 0 -5.5

GACTTTCATACCTGTGGCAT 3165 SEQ ID NO: 2166 -6.4 -24.7 71.6 -18.3 0 -4

TAAGTACTGTTAAAAATAAT 3378 SEQ ID NO: 2167 -6.4 -12.2 43.9 -5.8 10 -6.3

AAATCCAGAATTCATAAAGT 76 SEQ ID NO: 2168 -6.3 -16.3 51.9 -10 0 -7.4

AGCACCAATAGGTGTAAGTC 293 SEQ ID NO: 2169 -6.3 -22.6 67.4 -13 -3.3 -8.4

GAGCCAGTCCCAGGGCTTCC 384 SEQ ID NO: 2170 -6.3 -33 89.8 -23.9 -2.8 -7.8

TGGCCCTGTTCCCCATGCGA 406 SEQ ID NO: 2171 -6.3 -33.5 85 -26.3 -0.7 -6.6

AGGTAGGCCTTTGGAGGCAG 896 SEQ ID NO: 2172 -6.3 -27.7 79.6 -17 -4.4 -9.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTTAGCCTGGACTTGAGGCT 1187 SEQ ID NO: 2173 -6.3 -26.1 75 -16.7 -3.1 -8.8

TGCAAATAGGCCATGATTTT 1204 SEQ ID NO: 2174 -6.3 -21.4 62.4 -14.6 0 -7.7

CAGCTTCATTTGGTCATCAA 1355 SEQ ID NO: 2175 -6.3 -22.7 67.9 -15.9 -0.1 -4.7

GATTAAGAGCTCACTCCAGC 1385 SEQ ID NO: 2176 -6.3 -24.1 70.8 -16.3 -1.4 -9:3

CATTGACTTGTTCCTGGACA 1659 SEQ ID NO: 2177 -6.3 -23.9 69.5 -17 -0.3 -6.2

AAGTAGCTGTCCAAATTTCT 1724 SEQ ID NO: 2178 -6.3 -21.3 64 -15 0 -4.8

TTCAATCCACTCCATTACAA 2124 SEQ ID NO: 2179 -6.3 -21.8 63.4 -15.5 0 -1.7

CATAGTGGAGATCAGTTTAA 2202 SEQ ID NO: 2180 -6.3 -19.5 60.9 -13.2 0 -5.4

GCTTTACCATGGAGGAATCC 2282 SEQ ID NO: 2181 -6.3 -24.8 70.3 -16.5 -2 -8.8

TTTAGCTATGGAGCATTTGC 2653 SEQ ID NO: 2182 -6.3 -22.6 67.9 -13.8 -2.5 -6.7

GCAAGAATGAACCTTGAGTC 2929 SEQ ID NO: 2183 -6.3 -21 62.1 -13.2 -1.4 -5.1

TGAATTACTTTAATATCTTT 3007 SEQ ID NO: 2184 -6.3 -15.2 50.8 -8.9 0 -3.2

TAAACAAATGTTGATCCACA 3223 SEQ ID NO: 2185 -6.3 -17.7 54.2 -10.7 -0.4 -6.4

TTTTAAACAAATGTTGATCC 3226 SEQ ID NO: 2186 -6.3 -16.4 52.2 -9.4 -0.4 -5.9

TTTTCCAACATTAGTGACCT 25 SEQ ID NO: 2187 -6.2 -22.3 65.4 -16.1 0 -3.3

GAAAAGTGCAGCTTGTCAAA 169 SEQ ID NO: 2188 -6.2 -19.9 59.6 -12.4 -1.2 -7.9

TCCCCAGTATCTGAATTAGA 250 SEQ ID NO: 2189 -6.2 -23.6 68.2 -16.8 -0.3 -4.1

ATCCGTGTCGGTCCGGAAGC 315 SEQ ID NO: 2190 -6.2 -29.3 77.9 -20.7 -2.4 -11.4

CTGTTCCCCATGCGATCGAG 401 SEQ ID NO: 2191 -6.2 -28.3 75.1 -21.4 0 -8.8

TCACCATTTTAAATTGAGAC 447 SEQ ID NO: 2192 -6.2 -18.1 56.1 -11.9 0 -5.4

TACATGTGTACCTTTTATTA 591 SEQ ID NO: 2193 -6.2 -19.6 60.8 -13.4 0 -6.7

CAAACTTATTCCTTCCTCCA 729 SEQ ID NO: 2194 -6.2 -24.1 68.1 -17.9 0 -1.3

AGAGGGCATAGCTTGGATCA 839 SEQ ID NO: 2195 -6.2 -24.9 73 -18.7 0.4 -5.2

AATTGCAGAGGAAATGGTCA 863 SEQ ID NO: 2196 -6.2 -20.4 60.9 -13.7 -0.2 -5.4

GCTCACACTTCAAAAGTTCC 1161 SEQ ID NO: 2197 -6.2 -22.6 66.3 -15.5 -0.7 -4.2

CTCAAATCCCCCGCTGTATA 2256 SEQ ID NO: 2198 -6.2 -27.1 72 -20.9 0 -3.1

GACACTCAAATTAGGCTGTT 2455 SEQ ID NO: 2199 -6.2 -21.3 63.8 -15.1 0 -3.7

TCATGAACACGAGACAAAAC• 2553 SEQ ID NO: 2200 -6.2 -17.1 52.6 -10.9 0 -5.9

CATCATGAACACGAGACAAA 2555 SEQ ID NO: 2201 -6.2 -18.3 54.9 -12.1 0 -6.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GACATCCTAGCAAAATGTGT 2823 SEQ ID NO: 2202 -6.2 -21.3 62.7 -14.2 -0.8 -4.4

TCCTTTCTCTTTGCATAGAT 2890 SEQ ID NO: 2203 -6.2 -23.1 69.7 -16.9 0 -3.7

ATTTGAATTACTTTAATATC 3010 SEQ ID NO: 2204 -6.2 -14.3 48.9 -8.1 0 -2.7

TTTTAAAATTGTGAAATAAG 3189 SEQ ID NO: 2205 -6.2 -11.4 42.4 -4.3 -0.8 -6.5

GTACTGTTAAAAATAATTAC 3375 SEQ ID NO: 2206 -6.2 -13.2 46.1 -7 0 -4.4

GTTCCCCATGCGATCGAGCC 399 SEQ ID NO: 2207 -6.1 -31.2 80.8 -24.4 -0.1 -8.8

CTTGCATGTTTTCCGGCATC 426 SEQ ID NO: 2208 -6.1 -26.3 74.4 -19.3 -0.7 -6.3

ACACGGGACAAAGCTCTTCC 489 SEQ ID NO: 2209 -6.1 -24.9 69.3 -18.8 0 -4.8

GTCAGGTCAGAGGGCATAGC 847 SEQ ID NO: 2210 -6.1 -26.8 80.2 -20.7 0 -4

GGCTCATCTGGCTCACACTT 1171 SEQ ID NO: 2211 -6.1 -27.4 79.3 -20.4 -0.8 -4.4

TGGCCCACTCGACAATGGAG 1305 SEQ ID NO: 2212 -6.1 -26.6 71.6 -19.7 -0.6 -7

ATACTACTCCTGGCCCACTC 1315 SEQ ID NO: 2213 -6.1 -28.1 78 -22 0 -6.6

AATGTGGTCGAGGATTAAGA 1397 SEQ ID NO: 2214 -6.1 -20.2 60.7 -14.1 0 -4.9

GAGAACGAAGTTTTGCCACT 1545 SEQ ID NO: 2215 -6.1 -22.5 64.4 -14.6 -1.8 -8.6

CTGTCCAAATTTCTCTGTCT 1718 SEQ ID NO: 2216 -6.1 -23.1 69 -17 0 -4.5

TCCACTCCATTACAATGTCT 2119 SEQ ID NO: 2217 -6.1 -23.8 68.9 -17.7 0 -5.1

CTATTGTAGGTACAGCTGAT 2328 SEQ ID NO: 2218 -6.1 -21.9 66.8 -15.1 0 -9.1

CATTTTCTTAACATCATGAA

2566 SEQ ID NO: 2219 -6.1 -17.3 54.8 -11.2 0 -6.9 GCATTTTCTTAACATCATGA

2567 SEQ ID NO: 2220 -6.1 -19.8 60.7 -13.7 0 -6.5 AAGCCACATTTCAGCAACAG

2697 SEQ ID NO: 2221 -6.1 -22.7 65.4 -15.8 -0.6 -4.1

ACTTGGATGATGAAAAAGAC 2774 SEQ ID NO: 2222 -6.1 -16.2 51.6 -10.1 0 -3.2

AATTACTTTAATATCTTTCC 3005 SEQ ID NO: 2223 -6.1 -17 54.7 -10.9 0 -2.6

CACTATATCTTATTTGACTT 3264 SEQ ID NO: 2224 -6.1 -18.3 58 -12.2 0 -2.4

CTCAGGACCTAAAGAATGTA 3286 SEQ ID NO: 2225 -6.1 -20 59.9 -13.9 10 -3.8

TGCTATTTTGTTATATCACA 3319 SEQ ID NO: 2226 -6.1 -19.4 60.7 -13.3 0 -3.6

TAATTAAGTACTGTTAAAAA 3382 SEQ ID NO: 2227 -6.1 -12.3 44.2 -6.2 0 -6.3

GAAGGACACATCAGACTACA 135 SEQ ID NO: 2228 -6 -20.9 62.5 -14.2 -0.4 -2.8

CCATTTTAAATTGAGACACT 444 SEQ ID NO: 2229 -6 -18.6 56.7 -12.6 0 -5.4

ACAGCTTCTAGCTTCATTCC 691 SEQ ID NO: 2230 -6 -25.1 74.8 -17.3 -1.8 -6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTGTACATTGGCCCAAACTT 742 SEQ ID NO: 2231 -6 -23.5 66.4 -17.5 0 -6.6

GGATCACCTGAGACATGGCT 825 SEQ ID NO: 2232 -6 -26 73.6 -19.5 -0.2 -5.6

AGGAAAGTGGCCATATGTTT 1019 SEQ ID NO: 2233 -6 -22.4 65.6 -15.6 -0.3 -9

ACTTGAGGCTCATCTGGCTC 1177 SEQ ID NO: 2234 -6 -26.4 78 -19.5 -0.8 -5

TGGTCGAGGATTAAGAGCTC 1393 SEQ ID NO: 2235 -6 -22.8 67.7 -16.3 0 -8

ACTTGTCGGTAAATGTGGTC 1408 SEQ ID NO: 2236 -6 -22.3 66.5 -16.3 0 -3

TCTAAACTAAAGAGCACCAA 1603 SEQ ID NO: 2237 -6 -18.3 55.4 -12.3 0 -4.1

GAAGTAGCTGTCCAAATTTC 1725 SEQ ID NO: 2238 -6 -21 63.4 -15 0 -4.5

AGTAGAGGTATTCTTCAGCC 1779 SEQ ID NO: 2239 -6 -24 73.4 -17.4 -0.3 -3.3

TCCCCGTTCAGGTGCTTGTA 1798 SEQ ID NO: 2240 -6 -29.7 82.1 -22.3 -1.3 -4.4

CATCCCCGTTCAGGTGCTTG 1800 SEQ ID NO: 2241 -6 -29.5 80.1 -23.5 0.4 -4.4

AGGGCACATCCCCGTTCAGG 1806 SEQ ID NO: 2242 -6 -30.6 81.7 -22.6 -2 -6.4

TCCCCACTCCCCCAATCTCT 1906 SEQ ID NO: 2243 -6 -33.2 84.8 -27.2 0 -1.1

CTTCATAGTGGAGATCAGTT 2205 SEQ ID NO: 2244 -6 -21.8 67.5 -15.8 0 -5.5

TTGTAGGTACAGCTGATGCA 2325 SEQ ID NO: 2245 -6 -23.8 70.9 -16.2 -1.6 -9.1

GAACATATTTAAATGGCAAG 2525 SEQ ID NO: 2246 -6 -16 51.1 -9.5 -0.1 -6.4

TTTTCTTAACATCATGAACA 2564 SEQ ID NO: 2247 -6 -17.5 55.3 . -11.5 0 -6.9

TAGATTAACATGCGTCAATT 2875 SEQ ID NO: 2248 -6 -18.6 56.9 -12.6 0 -5

TCTTGAGGATGTTCAATTGC 2950 SEQ ID NO: 2249 -6 -21.4 65.2 -14.6 -0.6 -6.4

CTGTAAACCATGTATCCAGT 4 SEQ ID NO: 2250 -5.9 -22.5 65.6 -16.6 0 -4.3

TTGAGCAAAAGAAAAGTGCA 179 SEQ ID NO: 2251 -5.9 -17.3 53.4 -9.6 -1.8 -5.2

TAGAAGACATTCTTAGTGAA 234 SEQ ID NO: 2252 -5.9 -17.4 55.7 -10.1 -1.3 -4.6

CCATGCGATCGAGCCAGTCC 394 SEQ ID NO: 2253 -5.9 -29.8 78.5 -23.4 -0.1 -8.1

CCCTGTTCCCCATGCGATCG 403 SEQ ID NO: 2254 -5.9 -31.7 80 -25.3 0 -8.3

TCTGGCCCTGTTCCCCATGC 408 SEQ ID NO: 2255 -5.9 -33.4 88.1 -27.5 0 -6.6

TTACAGCTTCTAGCTTCATT 693 SEQ ID NO: 2256 -5.9 -22.5 68.9 -14.8 -1.8 -6

GGCCCTGTCTCTCTTGTACA 755 SEQ ID NO: 2257 -5.9 -28.9 83.2 -23 0 -6

CAGGGCCCTGTCTCTCTTGT• 758 SEQ ID NO: 2258 -5.9 -30.2 86.3 -21.1 0 -14.6

TCGGATGAGGGCTTTTTTCT 785 SEQ ID NO: 2259 -5.9 -24.5 71.5 -18.6 0 -3.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TGGTCAGGTCAGAGGGCATA

849 SEQ ID NO: 2260 -5.9 -26.2 77.6 -20.3 0 -4 GTAGGCCTTTGGAGGCAGAG

894 SEQ ID NO: 2261 -5.9 -27.1 78.2 -16.8 -4.4 -9.9 ATTTTGCACATAAGCCCAAA

1267 SEQ ID NO: 2262 -5.9 -21.8 62.1 -15.9 0 -5 CCTGGCCCACTCGACAATGG

1307 SEQ ID NO: 2263 -5.9 -28.9 75.2 -22.5 -0.2 -6.6 GGAAGATGGATCCTTCCTTT

1437 SEQ ID NO: 2264 -5.9 -24.4 70. ϊ -15.8 -2.7 -10.9 ATGCTATTATGGAATAGTCC

1476 SEQ ID NO: 2265 -5.9 -20.6 62.5 -12.8 -1.9 -6.8 ACCGTGTTGGTATCCATCTG

2148 SEQ ID NO: 2266 -5.9 -26 73.8 -19.1 -0.9 -4.6 CTGTTCATGATTTGGTGGAG

2440 SEQ ID NO: 2267 -5.9 -22.3 67.4 -16.4 0 -6.4 AAAGACTGATGTATACTAAC

2760 SEQ ID NO: 2268 -5.9 -15.8 51.5 -9.9 0 -6.3 GACACATGTAAAAATCACCA

2983 SEQ ID NO: 2269 -5.9 -18.5 55.6 -12.6 0 -6.5 ATTGTGAAATAAGGCAAGAC

3182 SEQ ID NO: 2270 -5.9 -17.3 54.1 -10.8 -0.3 -4.3 GTCCCAGGGCTTCCGTCTCC

378 SEQ ID NO: 2271 -5.8 -33.6 90.9 -26.5 -1.2 -6.8 ATCTGGCCCTGTTCCCCATG

409 SEQ ID NO: 2272 -5.8 -31.6 83.7 -25.8 0 -6.6 ACATTTTTGAAAACGACAGT

662 SEQ ID NO: 2273 -5.8 -17.5 54 -11.1 -0.3 -5.2 GCATAGCTTGGATCACCTGA

834 SEQ ID NO: 2274 -5.8 -25.6 73.2 -18.8 -0.9 -6.8 TACTCAGACTTGATGGCCCG

1042 SEQ ID NO: 2275 -5.8 -26.1 72 -19.6 -0.3 -8.3 ATCTGCCATTTTGCACATAA

1274 SEQ ID NO: 2276 -5.8 -22.5 65.4 -15.9 -0.6 -5 CACTCGACAATGGAGAAGAG

1300 SEQ ID NO: 2277 -5.8 -20.1 59.5 -13.5 -0.6 -5 CAGTTCTGAAGCAGCTTCAT

1366 SEQ ID NO: 2278 -5.8 -23.6 70.4 -15.1 -2.1 -13.4 CCGTTCAGGTGCTTGTAGTA

1795 SEQ ID NO: 2279 -5.8 -26.2 76.4 -20.4 0 -4.4 GGGCACATCCCCGTTCAGGT

1805 SEQ ID NO: 2280 -5.8 -31.8 84.9 -24.7 -1.2 -6.4 ATACAAGAACCGTTCTGTCC

2180 SEQ ID NO: 2281 -5.8 -23 65.9 -16.3 -0.7 -8.7 GATGTATACTAACAAGACTT

2753 SEQ ID NO: 2282 -5.8 -17.3 54.9 -11.5 0 -6.3 AAAAGACTGATGTATACTAA

2761 SEQ ID NO: 2283 -5.8 -14.9 49.4 -9.1 10 -6.3 GCGTCAATTTTGTTTCCAAC

2864 SEQ ID NO: 2284 -5.8 -22.5 65.5 -16.2 -0.2 -3.9 CTTTCTCTTTGCATAGATTA

2888 SEQ ID NO: 2285 -5.8 -20.5 63.8 -14.7 0 -3.5 GAATGAACCTTGAGTCAATA

2925 SEQ ID NO: 2286 -5.8 -18.9 57.5 -12.6 0 -7.6 CAAGAATGAACCTTGAGTCA

2928 SEQ ID NO: 2287 -5.8 -19.9 59.4 -13.2 -0.7 -5.5 TCAATTGCAGCAAGAATGAA

2938 SEQ ID NO: 2288 -5.8 -18.6 56.4 -12.1 0 -8.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CCTTTTAAAATTGTGAAATA 3191 SEQ ID NO: 2289 -5.8 -15 49.1 -8.3 -0. 8 -6.7

AATGTAAACACTATATCTTA 3272 SEQ ID NO: 2290 -5.8 -15.3 50.6 -9.5 0 -4.2

ACTTGCATGTTTTCCGGCAT

427 SEQ ID NO: 2291 -5.7 -26.1 73.3 -19.5 -0. 7 -6.3 CACTTGCATGTTTTCCGGCA

428 SEQ ID NO: 2292 -5.7 -26.8 74.4 -20.4 -0. 5 -6:5 GTCAGAGGGCATAGCTTGGA

842 SEQ ID NO: 2293 -5.7 -26.1 76.7 -19.7 -0. 4 -5.1

GGCTAGGAAAGTGGCCATAT 1023 SEQ ID NO: 2294 -5.7 -24.6 69.9 -17.2 -1. 7 -9

GGATTAAGAGCTCACTCCAG 1386 SEQ ID NO: 2295 -5.7 -23.5 69.1 -16.3 -1. 4 -9.3

TCGGTAAATGTGGTCGAGGA 1403 SEQ ID NO: 2296 -5.7 -23.1 66.2 -17.4 0 -4.9

CGAAGAAGTAGCTGTCCAAA 1729 SEQ ID NO: 2297 -5.7 -21.1 61.2 -15.4 0 -4.8

GATTCACAGTTTGCAATACA 2066 SEQ ID NO: 2298 -5.7 -20.5 62.2 -14.3 0 -8.1

TGATTTGGTGGAGCTACCAC 2433 SEQ ID NO: 2299 -5.7 -24.5 71 -15.8 -3 -11.6

CATATTAATAGAATTTCCTA 2501 SEQ ID NO: 2300 -5.7 -16.3 52.6 -10.6 0 -5.9

TGATGTATACTAACAAGACT

2754 SEQ ID NO: 2301 -5.7 -17.2 54.6 -11.5 0 -6.3 CTGATGTATACTAACAAGAC

2755 SEQ ID NO: 2302 -5.7 -17.2 54.6 -11.5 0 -5.6 ACTGATGTATACTAACAAGA

2756 SEQ ID NO: 2303 -5.7 -17.2 54.6 -11.5 0 -6.3 GACTGATGTATACTAACAAG

2757 SEQ ID NO: 2304 -5.7 -17.2 54.6 -11.5 0 -6.3 CATCCTTTCCTTTCTCTTTG

2897 SEQ ID NO: 2305 -5.7 -24.5 72.5 -18.8 0 -1

TTCTTTGTCCTCCCATATTT 3101 SEQ ID NO: 2306 -5.7 -25.1 73 -19.4 0 -2.1

AATGTTGATCCACATCTGCA 3217 SEQ ID NO: 2307 -5.7 -23 67 -16.5 -0. 6 -4.9

GACTCTGTACTTTTTCCAAC 36 SEQ ID NO: 2308 -5.6 -22 66.2 -16.4 0 -4.8

TTCCCTGGACTCTGTACTTT 43 SEQ ID NO: 2309 -5.6 -25.8 74.8 -20.2 0 -4.8

AGAAAAGTGCAGCTTGTCAA 170 SEQ ID NO: 2310 -5.6 -20.6 61.8 -13 -2 -8.7

TCCACTTTGGGCAGCATGAC 361 SEQ ID NO: 2311 -5.6 -26.6 75.2 -18.5 -2. 5 -7.6

GGAGGCAGAGTGGATGTTTT 884 SEQ ID NO: 2312 -5.6 -24.6 73.3 -19 0 -4

TAGGAAAGTGGCCATATGTT 1020 SEQ ID NO: 2313 -5.6 -22 64.7 -15.6 -0. 3 -9

CTTCGGTTAGCCTGCTCTTG 1225 SEQ ID NO: 2314 -5.6 -27.2 77.5 -20.8 -0. 6 -5.3

CTGAAGCAGCTTCATTTGGT 1361 SEQ ID NO: 2315 -5.6 -23.8 70.2 -15.5 -2. 1 -13.4

TGTTGCCCAGTAACCAGGAA 1453 SEQ ID NO: 2316 -5.6 -26 71.7 -19.7 -0. 5 -4.2

CTAAACTAAAGAGCACCAAG 1602 SEQ ID NO: 2317 -5.6 -17.9 54.4 -12.3 0 -4.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TCCAAATTTCTCTGTCTGCT 1715 SEQ ID NO: 2318 -5.6 -23.7 70 -18.1 0 -4.5

TAGTAGAGGTATTCTTCAGC 1780 SEQ ID NO: 2319 -5.6 -21.7 68.7 -15.6 -0.1 -2.9

CCTTTTTAAATTCAATATCT 1999 SEQ ID NO: 2320 -5.6 -17.1 54.1 -11.5 0 -4.5

CAATACAAATACCCTGATAC 2053 SEQ ID NO: 2321 -5.6 -18.5 55.4 -12.9 0 -1.9

ATGAAATCCAACAATGCCAA 2716 SEQ ID NO: 2322 -5.6 -19.6 56.7 -14 0 -3

ATGTATACTAACAAGACTTC 2752 SEQ ID NO: 2323 -5.6 -17.1 54.9 -11.5 0 -6.3

TGCAGCAAGAATGAACCTTG 2933 SEQ ID NO: 2324 -5.6 -21.3 61.6 -15.1 -0.3 -6

CAATTGCAGCAAGAATGAAC 2937 SEQ ID NO: 2325 -5.6 -18.4 55.7 -12.1 0 -8.8

AAGTATTAATACTTTATTTT 3242 SEQ ID NO: 2326 -5.6 -14.3 49.1 -6.5 -1.1 ^• -12.4

CAGGACCTAAAGAATGTAAA 3284 SEQ ID NO: 2327 -5.6 -17.3 53.3 -11.7 0 -3.5

CAGTCCCAGGGCTTCCGTCT 380 SEQ ID NO: 2328 -5.5 -31.9 86.9 -25.1 -1.2 -7.2

ATTTTAAATTGAGACACTTG 442 SEQ ID NO: 2329 -5.5 -16 52 -10.5 0 -4.5

CACGGGACAAAGCTCTTCCA 488 SEQ ID NO: 2330 -5.5 -25.4 69.8 -18.8 -1 -6.8

TGGATcACCTGAGACATGGC 826 SEQ ID NO: 2331 -5.5 -25.1 71.5 -18.6 -0.9 -6.4

TGAGGGGGCATTGTCATGCT 979 SEQ ID NO: 2332 -5.5 -27 77.5 -18.4 -3.1 -7.1

TTTGATCTGCCATTTTGCAC 1278 SEQ ID NO: 2333 -5.5 -23.6 69 -17.3 -0.6 -5.9

CTCCTGGCCCACTCGACAAT 1309 SEQ ID NO: 2334 -5.5 -29 76.3 -23.5 0 -5.9

TTAAGTTCTCTGAAGAAGAT 1333 SEQ ID NO: 2335 -5.5 -17.4 55.8 -10.9 -0.9 -5.9

ACCAAGAATTTCAGACATAC 1588 • SEQ ID NO: 2336 -5.5 -18.8 57.4 -13.3 0 -4.3

GTCGAAGAAGTAGCTGTCCA 1731 SEQ ID NO: 2337 -5.5 -24.1 70 -17.8 -0.6 -5.8

GGCACATCCCCGTTCAGGTG 1804 SEQ ID NO: 2338 -5.5 -30.6 82.1 -24.6 -0.1 -4.6

ATTTAAATGGCAAGCTAACA 2519 SEQ ID NO: 2339 -5.5 -18.1 55.4 -12.6 0 -5.8

ATGTTGTATTTTTAAATGAA 2800 SEQ ID NO: 2340 -5.5 -14.8 49.7 -9.3 0 -4.5

AGATTAACATGCGTCAATTT 2874 SEQ ID NO: 2341 -5.5 -19 57.7 -13.5 10 -5

GATAATAGTCATTTGAAGAA 3128 SEQ ID NO: 2342 -5.5 -15.6 51.3 -10.1 0 -3.9

TATATCTTATTTGACTTTAA 3261 SEQ ID NO: 2343 -5.5 -15.6 52 -10.1 0 -2.4

AAGGACACATCAGACTACAG 134 SEQ ID NO: 2344 -5.4 -20.3 61.4 -14.2 -0.4 -2.8

AGCAAAAGAAAAGTGCAGCT 176 SEQ ID NO: 2345 -5.4 -19.3 57.6 -12.1 -1.8 -7.3

ACCCAGACACTTTATCTCCA 510 SEQ ID NO: 2346 -5.4 -25.8 72.6 -20.4 0 -2.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo ATTTTTGAAAACGACAGTAA 660 SEQ ID NO: 2347 -5.4 -15.6 50.2 -10.2 0 -5.2

AGTCCATTGGCTCGGATGAG 796 SEQ ID NO: 2348 . -5.4 -25.9 73.7 -19.5 -0.9 0 CAGAGGGCATAGCTTGGATC

840 SEQ ID NO: 2349 -5.4 -24.9 73 -18.8 -0.4 -5.1 TCAGAGGGCATAGCTTGGAT

841 SEQ ID NO: 2350 -5.4 -24.9 73 -18.8 -0.4 -5:i ATATGAATAGCCCATTATGG

1091 SEQ ID NO: 2351 -5.4 -20.8 61.1 -14.7 -0.4 -5

TCGTCTGGTAACTATCCATA 1110 SEQ ID NO: 2352 -5.4 -22.7 66.8 -16.8 -0.2 -3.7

TTCAGGTGCTTGTAGTAGAG 1792 SEQ ID NO: 2353 -5.4 -22.8 71 -17.4 0 -3.7

AGTACTTTTTTTCTTCCTGT 1938 SEQ ID NO: 2354 -5.4 -22.5 69.7 -17.1 0 -5.5

TTAATTAGCGTTACTTGGAG 1966 SEQ ID NO: 2355 -5.4 -19.5 59.7 -14.1 0 -4.1

ATCATGAACACGAGACAAAA 2554 SEQ ID NO: 2356 -5.4 -16.9 52.1 -11.5 0 -6.9

TTTCTTAACATCATGAACAC 2563 SEQ ID NO: 2357 -5.4 -17.6 55.5 -12.2 0 -6.9

CCAGAAATTTTTTATGAAAT 2729 SEQ ID NO: 2358 -5.4 -15.3 49.7 -9.1 -0.6 -6

GAAAAAGACTGATGTATACT 2763 SEQ ID NO: 2359 -5.4 -15.8 51.1 -10.4 0 -6.3

TTTCTCTTTGCATAGATTAA 2887 SEQ ID NO: 2360 -5.4 -18.9 59.6 -13.5 0 -3.7

AGGATGTTCAATTGCAGCAA 2945 SEQ ID NO: 2361 -5.4 -21.9 64.8 -15.9 0 -8.5

TGTTAATAATACTGATAATA 3141 SEQ ID NO: 2362 -5.4 -13.4 ^'46.6 -8 0 -3.2

TTTAAACAAATGTTGATCCA 3225 SEQ ID NO: 2363 -5.4 -17 53.1 -10.9 -0.4 -6.4

TTTCCAACATTAGTGACCTG 24 SEQ ID NO: 2364 -5.3 -22.2 65 -16.9 0 -3.3

GCAAAAGAAAAGTGCAGCTT 175 SEQ ID NO: 2365 -5.3 -19.4 57.7 -13 -1 -6.8

CAGTATCTGAATTAGAAGAC 246 SEQ ID NO: 2366 -5.3 -17.3 55.4 -12 0 -3.6

TGTTCCCCATGCGATCGAGC 400 SEQ ID NO: 2367 -5.3 -29.2 77.3 -23.2 0 -8.8

GGCATCTGGCCCTGTTCCCC 412 SEQ ID NO: 2368 -5.3 -34.6 90.9 -27.5 -1.8 -6.6

AAAACGACAGTAAGGACAAC 653 SEQ ID NO: 2369 -5.3 -16.8 52 -10.8 -0.4 -3.9

CCTGTCTCTCTTGTACATTG 752 SEQ ID NO: 2370 -5.3 -24 72.1 -18.7 0 -6.3

ATTGCAGAGGAAATGGTCAG 862 SEQ ID NO: 2371 -5.3 -21.1 63.2 -15.3 -0.2 -5.4

GGCTGCCGTGAGGGGGCATT 987 SEQ ID NO: 2372 -5.3 -31.7 84.9 -23.6 -2.8 -9.4

TAGGCCATGATTTTAGCCTG 1198 SEQ ID NO: 2373 -5.3 -24.7 70.7 -17.2 -2.2 -8.1

GTTCTGAAGCAGCTTCATTT•

1364 SEQ ID NO: 2374 -5.3 -23.1 69.7 -15.1 -2.1 -13.4 AGTTCTGAAGCAGCTTCATT

1365 SEQ ID NO: 2375 -5.3 -23 69.6 -15.1 -1.9 -13.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CGGTAAATGTGGTCGAGGAT 1402 SEQ ID NO: 2376 -5.3 -22.7 64.8 -17.4 0 -4.9

TTGACTTGTTCCTGGACACC 1657 SEQ ID NO: 2377 -5.3 -25.4 72.6 -19.4 -0.5 -6.3

GAGCTCCTAGGGGTTGTAAC 1870 SEQ ID NO: 2378 -5.3 -25.6 74.9 -20.3 0.4 -8.3

ACAGATTCGGTGACCACAGG 2385 SEQ ID NO: 2379 -5.3 -24.8 70.1 -19.5 0 -6.1

AACATCATGAACACGAGACA 2557 SEQ ID NO: 2380 -5.3 -19.2 57.1' -13.9 0 -6.9

AAGAATGAACCTTGAGTCAA 2927 SEQ ID NO: 2381 -5.3 -18.5 56.4 -13.2 0 -7.3

GGACACATGTAAAAATCACC 2984 SEQ ID NO: 2382 -5.3 -19 56.8 -13.7 0 -6.5

ATTACTTTAATATCTTTCCA 3004 SEQ ID NO: 2383 -5.3 -18.4 57.9 -13.1 0 -2.6

TAAAGAATGTAAACACTATA 3277 SEQ ID NO: 2384 -5.3 -13.1 45.6 -7.8 0 -4.2

CAGAAATCATTGAGCAAAAG 188 SEQ ID NO: 2385 -5.2 -16.1 51.2 -10.9 0 -4.5

ATTCTTAGTGAAATTATAGG 226 SEQ ID NO: 2386 -5.2 -16.3 53.4 -10.4 -0.4 -3.5

AGTCCCAGGGCTTCCGTCTC 379 SEQ ID NO: 2387 -5.2 -31.6 87.9 -25.1 -1.2 -7

GGGCATAGCTTGGATCACCT 836 SEQ ID NO: 2388 -5.2 -27.4 77.3 -20.8 -1.3 -6.9

TAACCTTGCAGGCTGCCGTG 997 SEQ ID NO: 2389 -5.2 -28.4 76.3 -21.6 -1.4 -10.1

GGGTACTCAGACTTGATGGC 1045 SEQ ID NO: 2390 -5.2 -24.9 73.4 -19.1 -0.3 -6

TTATGGACTCGGGTGAGCTG 1077 SEQ ID NO: 2391 -5.2 -24.8 71.4 -18.2 -1.3 -5.6

GCAAATAGGCCATGATTTTA 1203 SEQ ID NO: 2392 -5.2 -21.1 61.9 -15.4 0 -7.7

AGCTTTTCGTGCTTGCTTCG 1240 SEQ ID NO: 2393 -5.2 -26.2 74.8 -20.3 -0.5 -5.9

TCTGAAGCAGCTTCATTTGG 1362 SEQ ID NO: 2394 -5.2 -23 68.4 -15.1 -2.1 -13.4

GTGGTCGAGGATTAAGAGCT 1394 SEQ ID NO: 2395 -5.2 -23.6 69.4 -18.4 0 -5

ATGTGGTCGAGGATTAAGAG 1396 SEQ ID NO: 2396 -5.2 -20.9 63 -15.7 0 -4.9

AGAACGAAGTTTTGCCACTA 1544 SEQ ID NO: 2397 -5.2 -21.6 62.7 -14.6 -1.8 -8.6

AGAGAACGAAGTTTTGCCAC 1546 SEQ ID NO: 2398 -5.2 -21.6 62.8 -14.6 -1.8 -8.6

GTTGATCAAACTGGAGAGAA 1560 SEQ ID NO: 2399 -5.2 -19 58.2 -12.9 -0.3 -9.4

TGTCCAAATTTCTCTGTCTG 1717 SEQ ID NO: 2400 -5.2 -22.2 66.9 -17 0 -4.3

TTCAATGAGAAGGTTATTAT 1826 SEQ ID NO: 2401 -5.2 -17 54.7 -11.8 0 -5

CCTAAATTTCTTCATAGTGG 2214 SEQ ID NO: 2402 -5.2 -20 60.9 -14.8 0 -4.9

GTACAGCTGATGCATTCTTG 2319 SEQ ID NO: 2403 -5.2 -23.1 69.1 -16.9 -0.8 -9.1

TATTGTAGGTACAGCTGATG 2327 SEQ ID NO: 2404 -5.2 -21 64.6 -15.1 0 -9.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CGGTGACCACAGGGCAGAGG 2378 SEQ ID NO: 2405 -5.2 -28.3 77 -22.2 -0.8 -6.1

AGACTGATGTATACTAACAA 2758 SEQ ID NO: 2406 -5.2 -17.2 54.6 -12 0 -6.3

TGTGACTATTTGACATCCTA 2834 SEQ ID NO: 2407 -5.2 -21.3 64.2 -16.1 0 -2.9

TGAAGAATTTGCGATTCTTT 3115 SEQ ID NO: 2408 -5.2 -18.8 57.4 -10.2 -3.4 -8.'6

TGAAATAAGGCAAGACTTTC 3178 SEQ ID NO: 2409 -5.2 -17.5 54.7 -12.3 0 -4

AATTAAGTACTGTTAAAAAT 3381 SEQ ID NO: 2410 -5.2 -12.6 44.7 -7.4 0 -5.8

AAAATTAAAGTCTAAATGAG 3439 SEQ ID NO: 2411 -5.2 -11.7 42.9 -6.5 0 -3.2

CTTTTTCCAACATTAGTGAC 27 SEQ ID NO: 2412 -5.1 -20.4 62 -15.3 0 -3.3

GTACTTTTTCCAACATTAGT 30 SEQ ID NO: 2413 -5.1 -20.7 63.4 -15.6 0 -4

CATCAGACTACAGTAACCCT 127 SEQ ID NO: 2414 -5.1 -23.4 67.4 -18.3 0 -3.6

GCAGCTTGTCAAATTTCGTG 162 SEQ ID NO: 2415 -5.1 -22.8 66.7 -17.7 0 -4.5

GAGCAAAAGAAAAGTGCAGC 177 SEQ ID NO: 2416 -5.1 -19 57 -12.1 -1.8 -5.7

CCATTGGCTCGGATGAGGGC 793 SEQ ID NO: 2417 -5.1 -28.5 77.7 -22 -1.3 0

GGCATAGCTTGGATCACCTG 835 SEQ ID NO: 2418 -5.1 -26.2 74.5 -19.7 -1.3 -6.8

TCAGGTCAGAGGGCATAGCT 846 SEQ ID NO: 2419 -5.1 -26.5 78.4 -20.7 -0.4 -4.4

ATGTTTGGTAACCTTGCAGG 1005 SEQ ID NO: 2420 -5.1 -23.7 69.1 -17.8 -0.6 -6.4

CATTTTGCACATAAGCCCAA 1268 SEQ ID NO: 2421 -5.1 -23.2 65.1 -17.6 -0.1 -4.7

CATTTGGTCATCAACCTTAA 1349 SEQ ID NO: 2422 -5.1 -21 62.4 -14.8 -1 -4.7

GGGGTTGTAACTTATGCTCT 1861 SEQ ID NO: 2423 -5.1 -24 71.4 -18.9 0 -4.3

CCTAGGGGTTGTAACTTATG 1865 SEQ ID NO: 2424 -5.1 -22.6 66.8 -17.5 0 -7.4

AGAGCTCCTAGGGGTTGTAA 1871 SEQ ID NO: 2425 -5.1 -25.4 74.6 -19.6 -0.2 -8.4

CAAGCTAACATATTAATAGA 2509 SEQ ID NO: 2426 -5.1 -15.7 51 -10.6 0 -5.9

CAGAAATTTTTTATGAAATC 2728 SEQ ID NO: 2427 -5.1 -13.7 47 -8.1 -0.1 -6

ATAGATTAACATGCGTCAAT 2876 SEQ ID NO: 2428 -5.1 -18.5 56.6 -13.4 0 -5

AGCAAGAATGAACCTTGAGT 2930 SEQ ID NO: 2429 -5.1 -20.6 61 -14 -1.4 -5.1

TTGGGGAAGATTTGAATTAC 3019 SEQ ID NO: 2430 -5.1 -18.3 56.7 -13.2 0 -3.2

CCTCAGGACCTAAAGAATGT 3287 SEQ ID NO: 2431 -5.1 -22.3 64 -17.2 0 -3.8

AAGAAAAGTGCAGCTTGTCA 171 SEQ ID NO: 2432 -5 -20.6 61.8 -13.6 -2 -8.7

GTGTAAGTCCGTGCTTTAAA 282 SEQ ID NO: 2433 -5 -22.2 65.1 -16.7 -0.2 -4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TCCATATATGAATAGCCCAT 1096 SEQ ID NO: 2434 -5 -22.6 64.5 -17.1 0 -7.5

TCCTGGCCCACTCGACAATG 1308 SEQ ID NO: 2435 -5 -28.1 74.4 -23.1 0 -6.6

TTGGTCATCAACCTTAAGTT

1346 SEQ ID NO: 2436 -5 -21.5 64.5 -14.8 -1.7 -7.3 TTTGGTCATCAACCTTAAGT

1347 SEQ ID NO: 2437 -5 -21.5 64.5 -14.8 -1.7 -7.4 GAAGCAGCTTCATTTGGTCA

1359 SEQ ID NO: 2438 -5 -24 71.2 -17 -1.3 -11.9

TTGACATCTAAACTAAAGAG 1609 SEQ ID NO: 2439 -5 -15.2 50 -10.2 0 -2.9

AGGTTATTATAGGGCACATC 1816 SEQ ID NO: 2440 -5 -21.9 66.8 -16.9 0 -4

ATCCATCTGTGAGTTCAATC 2137 SEQ ID NO: 2441 -5 -22.3 67.7 -17.3 0 -3.2

CCTAATTAATAAGATTAGTT 2234 SEQ ID NO: 2442 -5 -15.7 51.3 -9.3 -1.3 ^• -5.2

GGTGACCACAGGGCAGAGGT 2377 SEQ ID NO: 2443 -5 -28.7 80.9 -22.8 -0.8 -6.1

AATTCACACTTACATAAGAT 2601 SEQ ID NO: 2444 -5 -16.8 53.6 -11.3 -0.2 -5

TGACATCCTAGCAAAATGTG 2824 SEQ ID NO: 2445 -5 -20.1 59.7 -14.2 -0.8 -4.4

TGCGTCAATTTTGTTTCCAA 2865 SEQ ID NO: 2446 -5 -22.3 64.8 -17.3 0 -4

TAATAGTCATTTGAAGAATT

3126 SEQ ID NO: 2447 -5 -15.1 50.3 -10.1 0 -3.9 CCAGAATTCATAAAGTTACA

72 SEQ ID NO: 2448 -4.9 -18 55.6 -13.1 0 -7.4

ATCCCCAGTATCTGAATTAG 251 SEQ ID NO: 2449 -4.9 -23 66.9 -18.1 0.2 -3.6

GCACCAATAGGTGTAAGTCC 292 SEQ ID NO: 2450 -4.9 -24.6 70.8 -16.4 -3.3 -8.4

CCAGTCCCAGGGCTTCCGTC 381 SEQ ID NO: 2451 -4.9 -33 88.3 -26.8 -1.2 -7.2

ATGTTTTCCGGCATCTGGCC 421 SEQ ID NO: 2452 -4.9 -28.7 79 -21.9 -1.9 -6.3

GGTGAGGAGCCCATAATGGT 530 SEQ ID NO: 2453 -4.9 -26.7 74.7 -20.9 -0.7 -5.4

TGAGCTGGTATAGGGGTCTG 1064 SEQ ID NO: 2454 -4.9 -25.2 75.1 -19.5 -0.6 -5

CAGTAACCAGGAAGATGGAT 1446 SEQ ID NO: 2455 -4.9 -21.3 62.5 -15.3 -1 -4.5

AGCACCAAGAATTTCAGACA 1591 SEQ ID NO: 2456 -4.9 -21.4 62.8 -16.5 0 -5.1

TCTGGGGCTGTGAAGCTTTG 2085 SEQ ID NO: 2457 -4.9 -25.6 74.3 -17.4 -3.3 -9.3

TCAGTTCAGCTTTACCATGG 2290 SEQ ID NO: 2458 -4.9 -24.2 71.6 -18.8 0 -8.3

ATTCACACTTACATAAGATG 2600 SEQ ID NO: 2459 -4.9 -17.5 55.4 -12.1 -0.2 -5

ATAATAGTCATTTGAAGAAT

3127 SEQ ID NO: 2460 -4.9 -15 50 -10.1 0 -3.9 ACTGTTAAAAATAATTACCA

3373 SEQ ID NO: 2461 -4.9 -15 49 -10.1 0 -4.4 TACTGTTAAAAATAATTACC

3374 SEQ ID NO: 2462 -4.9 -14 47.3 -9.1 0 -4.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GACACTTGCATGTTTTCCGG

430 SEQ ID NO: 2463 -4.8 -25.1 71 -19.8 -0.1 -6.8 TTTTAAATTGAGACACTTGC

441 SEQ ID NO: 2464 -4.8 -17.8 55.9 -13 0 -4.5

CACACGGGACAAAGCTCTTC 490 SEQ ID NO: 2465 -4.8 -23.6 66.9 -18.8 0 -5

GGTCAGAGGGCATAGCTTGG 843 SEQ ID NO: 2466 -4.8 -26.7 78 -21.2 -0.4 -5:1

CAGGTCAGAGGGCATAGCTT 845 SEQ ID NO: 2467 -4.8 -26.2 76.9 -20.7 -0.4 -4.6

AGGCCTTTGGAGGCAGAGTG 892 SEQ ID NO: 2468 -4.8 -27.4 78.6 -18.2 -4.4 -9.9

CGTCTGGTAACTATCCATAT 1109 SEQ ID NO: 2469 -4.8 -22.3 65.3 -16.8 -0.4 -3.6

GCCATGATTTTAGCCTGGAC 1195 SEQ ID NO: 2470 -4.8 -25.8 72.9 -20.5 -0.2 -4.7

GAGCACCAAGAATTTCAGAC 1592 SEQ ID NO: 2471 -4.8 -21.3 62.9 -16.5 0 -5.1

TCAATGAGAAGGTTATTATA 1825 SEQ ID NO: 2472 -4.8 -16.6 53.8 -11.8 0 -3.8

CAATCCACTCCATTACAATG 2122 SEQ ID NO: 2473 -4.8 -21.3 61.6 -16.5 0 -4.7

GGGCAGAGGTGCTCGGGCCT 2367 SEQ ID NO: 2474 -4.8 -32.9 89.1 -24.6 -3.5 -13.3

GCTAACATATTAATAGAATT 2506 SEQ ID NO: 2475 -4.8 -15.1 49.9 -10.3 0 -5.9

AAAGTTTGTAGTCATTTCCC 2629 SEQ ID NO: 2476 -4.8 -21.8 65.8 -17 0 -3.7

TTTGACATCCTAGCAAAATG 2826 SEQ ID NO: 2477 -4.8 -19.1 57.5 -13.8 -0.2 -4.1

GATTAACATGCGTCAATTTT 2873 SEQ ID NO: 2478 -4.8 -19.1 57.9 -14.3 0 -5

TTGCGATTCTTTGTCCTCCC 3107 SEQ ID NO: 2479 -4.8 -27.8 77.4 -23 0 -4.1

TAAACACTATATCTTATTTG 3268 SEQ ID NO: 2480 -4.8 -15 50.2 -10.2 0 -2.4

TAACATTAAGGAAATTACCG 3343 SEQ ID NO: 2481 -4.8 -16.2 50.8 -10.7 -0.5 -3.7

TGTTAAAAATAATTACCAAT 3371 SEQ ID NO: 2482 -4.8 -13.2 45.4 -8.4 0 -4.4

GATCCGTGTCGGTCCGGAAG 316 SEQ ID NO: 2483 -4.7 -28.1 75.1 -21 -2.4 -11.4

AGACACTTGCATGTTTTCCG

431 SEQ ID NO: 2484 -4.7 -23.9 68.7 -18.7 -0.1 -6.8 AGGAGCCCATAATGGTACCC

526 SEQ ID NO: 2485 -4.7 -27.6 74.7 -22 -0.7 -8.1

CACCTGAGACATGGCTTCTA 821 SEQ ID NO: 2486 -4.7 -24.9 71.5 -20.2 0 -5.2

TTTCAATGAGAAGGTTATTA 1827 SEQ ID NO: 2487 -4.7 -17.1 55 -11.8 -0.3 -5

GGGGCTATTGTAGGTACAGC 2332 SEQ ID NO: 2488 -4.7 -25.8 76.4 -20.6 -0.2 -5.2

GCTCGGGCCTTCAAAGGAAG 2357 SEQ ID NO: 2489 -4.7 -25.9 71.1 -18.6 -2.6 -11.8

TTCGGTGACCACAGGGCAGA- 2380 SEQ ID NO: 2490 -4.7 -27.6 76.2 -22.2 -0.3 -8.2

CATAAGATGAGGGATACTGC 2589 SEQ ID NO: 2491 -4.7 -20.5 61.6 -14.9 -0.7 -6.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TATTAATACTTTATTTTAAA 3239 SEQ ID NO: 2492 -4.7 -12.1 44.1 -7.4 0 -5

TCCCTGGACTCTGTACTTTT 42 SEQ ID NO: 2493 -4.6 -25.8 74.8 -21.2 0 -4.8

GTATCTGAATTAGAAGACAT 244 SEQ ID NO: 2494 -4.6 -17.3 55.2 -12.1 -0.3 -3.9

GACTTGATGGCCCGGCTAGG 1036 SEQ ID NO: 2495 -4.6 -29 77.8 -23.7 -0.4 -8.1

GTTGCCCAGTAACCAGGAAG 1452 SEQ ID NO: 2496 -4.6 -26 72.1 -21.4 0 -4

AGAGCACCAAGAATTTCAGA 1593 SEQ ID NO: 2497 -4.6 -21.1 62.6 -16.5 0 -5.1

GTAGGTACAGCTGATGCATT 2323 SEQ ID NO: 2498 -4.6 -23.8 71 -17.6 -1.6 -9.1

CTTTAGCTATGGAGCATTTG 2654 SEQ ID NO: 2499 -4.6 -21.7 65.5 -15.4 -1.7 -5.9

AGAAATAAGGTCTAAGTTGC 2673 SEQ ID NO: 2500 -4.6 -18 56.7 -13.4 0 -2.6

ATGCCAAAGCCACATTTCAG 2703 SEQ ID NO: 2501 -4.6 -23.8 66.9 -18.3 -0.7 -3.4

TCATTTGAAGAATTTGCGAT 3120 SEQ ID NO: 2502 -4.6 -18.5 56.5 -13.9 0 -4.8

TTCCAACATTAGTGACCTGC 23 SEQ ID NO: 2503 -4.5 -23.9 68.7 -19.4 0 -3.3

ATCGAGCCAGTCCCAGGGCT 387 SEQ ID NO: 2504 -4.5 -31.7 85.1 -24.6 -2.6 -8.6

CTGGCCCTGTTCCCCATGCG 407 SEQ ID NO: 2505 -4.5 -33.8 85.5 -28.4 -0.7 -6.6

TTGCAGAGGAAATGGTCAGG 861 SEQ ID NO: 2506 -4.5 -22.3 65.8 -17.3 -0.2 -5.4

CGGCTAGGAAAGTGGCCATA 1024 SEQ ID NO: 2507 -4.5 -25.4 70 -18.7 -2.2 -9

CTATCCATATATGAATAGCC 1099 SEQ ID NO: 2508 -4.5 -20.5 61.1 -16 0 -7

ATAGGCCATGATTTTAGCCT 1199 SEQ ID NO: 2509 -4.5 -24.7 70.8 -18.2 -2 -7.7

TACTCCTGGCCCACTCGACA 1311 SEQ ID NO: 2510 -4.5 -29.6 78.7 -25.1 0 -6.6

GAACGAAGTTTTGCCACTAA 1543 SEQ ID NO: 2511 -4.5 -20.9 60.6 -14.6 -1.8 -7.1

GTCCAAATTTCTCTGTCTGC 1716 SEQ ID NO: 2512 -4.5 -24 71.4 -19.5 0 -4.5

GCACATCCCCGTTCAGGTGC 1803 SEQ ID NO: 2513 -4.5 -31.2 83.9 -25.2 -1.4 -6.1

AATTAGCGTTACTTGGAGCA

1964 SEQ ID NO: 2514 -4.5 -22.2 65.2 -17.7 0.1 -4.1 TAATTAGCGTTACTTGGAGC

1965 SEQ ID NO: 2515 -4.5 -21.2 63.5 -16.7 10 -4.5 AGTCATTTCCCTTAATATTA

2620 SEQ ID NO: 2516 -4.5 -20.4 62.2 -15.9 0 -5.2

GAAATAAGGTCTAAGTTGCT 2672 SEQ ID NO: 2517 -4.5 -18.9 58.5 -14.4 0 -3.6

AAAGCCACATTTCAGCAACA 2698 SEQ ID NO: 2518 -4.5 -22 63.2 -16.7 -0.6 -4.1

CCAACAATGCCAAAGCCACA 2709 SEQ ID NO: 2519 -4.5 -24.7 65.7 -19.3 -0.7 -3.2

ACATGTAAAAATCACCATTT 2980 SEQ ID NO: 2520 -4.5 -17.2 53.4 -12.2 -0.2 -6.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AGATTTGAATTACTTTAATA

3012 SEQ ID NO: 2521 -4.5 -14.5 49.1 -10 0 -3.2 AAGATTTGAATTACTTTAAT

3013 SEQ ID NO: 2522 -4.5 -14.1 48 -9.6 0 -3.2 TCTACAGCAGACTTTGGTCT

3079 SEQ ID NO: 2523 -4.5 -24 72.4 -17.3 -2.2 0

GTGGCATCGCATGTTAATAA 3152 SEQ ID NO: 2524 -4.5 -21.9 63.8 -16.5 -0.7 -5:3

AAAATCCAGAATTCATAAAG 77 SEQ ID NO: 2525 -4.4 -14.4 47.7 -10 0 -7.4

GAATTAGAAGACATTCTTAG 238 SEQ ID NO: 2526 -4.4 -16.3 53.2 -10.8 -1 -6.2

TCCCAGGGCTTCCGTCTCCA 377 SEQ ID NO: 2527 -4.4 -33.1 88.1 -28 -0.4 -6.8

TCGAGCCAGTCCCAGGGCTT 386 SEQ ID NO: 2528^' -4.4 -31.8 85.6 -24.6 -2.8 -8

GGCCCTTACAGCTTCTAGCT 698 SEQ ID NO: 2529 -4.4 -29.1 82.1 -23 -1.7 -8.9

GGGCCCTGTCTCTCTTGTAC 756 SEQ ID NO: 2530 -4.4 -29.4 84.9 -24 0 -10

GCTTGGATCACCTGAGACAT 829 SEQ ID NO: 2531 -4.4 -24.9 71.4 -19.5 -0.9 -4.5

CAGACTTGATGGCCCGGCTA 1038 SEQ ID NO: 2532 -4.4 -28.5 76.4 -23.4 -0.4 -8.1

GCTTGCTTCGGTTAGCCTGC 1230 SEQ ID NO: 2533 -4.4 -29.5 82.7 -24.2 -0.7 -5.2

CCACTCGACAATGGAGAAGA 1301 SEQ ID NO: 2534 -4.4 -22.1 62.8 -16.9 -0.6 -5

CTTGTCGGTAAATGTGGTCG 1407 SEQ ID NO: 2535 -4.4 -22.9 66.1 -18.5 0 -2.8

GGAGAGAACGAAGTTTTGCC 1548 SEQ ID NO: 2536 -4.4 -22.5 64.8 -16.3 -1.8 -8.6

CCTGGACACCTTCTACCAGC 1647 SEQ ID NO: 2537 -4.4 -28.5 78.1 -22.2 -1.9 -6.3

GCAATACAAATACCCTGATA 2054 SEQ ID NO: 2538 -4.4 -20.1 58.6 -15.7 0 -3.4

TCGGTGACCACAGGGCAGAG 2379 SEQ ID NO: 2539 -4.4 -27.5 76.2 -22.2 -0.8 -8.2

AATGCCAAAGCCACATTTCA 2704 SEQ ID NO: 2540 -4.4 -23.1 64.7 -17.8 -0.7 -4.4

AAATCCAACAATGCCAAAGC 2713 SEQ ID NO: 2541 -4.4 -20.1 57.6 -15.1 -0.3 -3.1

GATTTGAATTACTTTAATAT 3011 SEQ ID NO: 2542 -4.4 -14.5 49 -10.1 0 -3.2

GGCATCGCATGTTAATAATA

3150 SEQ ID NO: 2543 -4.4 -20.4 60.4 -15.1 -0.7 -5.5 TGGCATCGCATGTTAATAAT

3151 SEQ ID NO: 2544 -4.4 -20.7 60.8 -15.4 -0.7 -5.3 CCTAAAGAATGTAAACACTA

3279 SEQ ID NO: 2545 -4.4 -16.3 51.4 -11.9 0 -4.2

GCTGTAAACCATGTATCCAG 5 SEQ ID NO: 2546 -4.3 -23.1 66.6 -18.8 0 -4.3

TGTACTTTTTCCAACATTAG 31 SEQ ID NO: 2547 -4.3 -19.5 60.1 -15.2 0 -4.8

TGTTTTCCGGCATCTGGCCC■ 420 SEQ ID NO: 2548 -4.3 -30.7 82.5 -24.1 -2.3 -6.6

TTTAAATTGAGACACTTGCA 440 SEQ ID NO: 2549 -4.3 -18.4 56.8 -14.1 0 -4.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AACGCTTTCTCTGTGTTTTG

636 SEQ ID NO: 2550 -4.3 -22.5 67.2 -17.5 -0.4 -4.2 AGACATTTTTGAAAACGACA

664 SEQ ID NO: 2551 -4.3 -16.9 52.6 -12 -0.3 -4.7

GGTCAGGTCAGAGGGCATAG 848 SEQ ID NO: 2552 -4.3 -26.2 78.2 -21.9 0 -4

AAATGGTCAGGTCAGAGGGC 852 SEQ ID NO: 2553 -4.3 -24.4 71.8 -20.1 0 -2.8

GAGAGAACGAAGTTTTGCCA 1547 SEQ ID NO: 2554 -4.3 -22 63. S -16.4 -1.2 -8.6

GCAACATTTCAATGAGAAGG 1833 SEQ ID NO: 2555 -4.3 -19 57.7 -14.1 -0.3 -5.8

TTCATAGTGGAGATCAGTTT 2204 SEQ ID NO: 2556 -4.3 -21 65.8 -16.7 0 -5.5

AAGCCTAATTAATAAGATTA

2237 SEQ ID NO: 2557 -4.3 -15.5 50.4 -11.2 0 -4.7 TAAGCCTAATTAATAAGATT

2238 SEQ ID NO: 2558 -4.3 -15.5 50.4 -11.2 0 -4.7 CATTTGCTTTGAAAGTTTGT

2640 SEQ ID NO: 2559 -4.3 -19.6 60.3 -15.3 0 -4.5

ACAATGCCAAAGCCACATTT 2706 SEQ ID NO: 2560 -4.3 -22.9 63.9 -17.9 -0.5 -4.1

GAAGATTTGAATTACTTTAA

3014 SEQ ID NO: 2561 -4.3 -14.7 49.3 -10.4 0 -3.2 GGAAGATTTGAATTACTTTA

3015 SEQ ID NO: 2562 -4.3 -16.6 53.5 -12.3 0 -3.2 AAAATAACATTAAGGAAATT

3347 SEQ ID NO: 2563 -4.3 -11.4 42.1 -7.1 0 -2.9

CATTAGTGACCTGCTGTAAA 17 SEQ ID NO: 2564 -4.2 -21.6 63.7 -17.4 0 -3.6

GGAAGGACACATCAGACTAC 136 SEQ ID NO: 2565 -4.2 -21.4 63.8 -17.2 0.3 -2.9

CAACGCTTTCTCTGTGTTTT

637 SEQ ID NO: 2566 -4.2 -23.2 68.6 -18.2 -0.6 -4.3 CATTTTTGAAAACGACAGTA

661 SEQ ID NO: 2567 -4.2 -17 53 -12.8 0 -5.2

ATTATGGACTCGGGTGAGCT 1078 SEQ ID NO: 2568 -4.2 -24.8 71.5 -19.2 -1.3 -5.6

CTTGAGGCTCATCTGGCTCA 1176 SEQ ID NO: 2569 -4.2 -26.9 78.4 -21.6 -1 -5

TTCGGTTAGCCTGCTCTTGC 1224 SEQ ID NO: 2570 -4.2 -28.1 80 -23.1 -0.6 -5.6

TCTGCCATTTTGCACATAAG 1273 SEQ ID NO: 2571 -4.2 -22.5 65.7 -17.5 -0.6 -5

ACTCCTGGCCCACTCGACAA 1310 SEQ ID NO: 2572 -4.2 -29.2 76.9 -25 0 -6.6

AGCTTCATTTGGTCATCAAC 1354 SEQ ID NO: 2573 -4.2 -22.2 67.3 -17.4 -0.3 -4.7

TGTGAGTTCAATCCACTCCA 2130 SEQ ID NO: 2574 -4.2 -24.8 71.7 -19.3 -1.2 -4.6

ATTGTTTCAGTTCAGCTTTA 2296 SEQ ID NO: 2575 -4.2 -21.6 67.7 -17.4 0 -4.5

AACTTGGATGATGAAAAAGA 2775 SEQ ID NO: 2576 -4.2 -15.3 49.5 -11.1 0 -3.2

ATGCGTCAATTTTGTTTCCA 2866 SEQ ID NO: 2577 -4.2 -23 67 -18.8 0 -4.6

TGATAATAGTCATTTGAAGA 3129 SEQ ID NO: 2578 -4.2 -16.3 53 -11.6 -0.1 -4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AGTATCTGAATTAGAAGACA 245 SEQ ID NO: 2579 -4.1 -17.3 55.4 -12 -1.1 -4.7

GACACTTTATCTCCACACAC 505 SEQ ID NO: 2580 -4.1 -22.9 67.4 -18.8 0 -1.8

CGCTTTCTCTGTGTTTTGTC 634 SEQ ID NO: 2581 -4.1 -24.6 74.3 -20.5 0 -3.1

GCAGGCTGCCGTGAGGGGGC 990 SEQ ID NO: 2582 -4.1 -33.4 89.4 -27.6 -1.7 -10'.1

CTTGCAGGCTGCCGTGAGGG 993 SEQ ID NO: 2583 -4.1 -30.2 81.9 -24.5 -1.5 -10.1

GCCCGGCTAGGAAAGTGGCC 1027 SEQ ID NO: 2584 -4.1 -30.8 80.2 -25.5 -1.1 -8.4

GCCTGCTCTTGCTGCAAATA 1216 SEQ ID NO: 2585 -4.1 -26.3 73.5 -20.6 -1.5 -9.3

TGGTCATCAACCTTAAGTTC 1345 SEQ ID NO: 2586 -4.1 -21.8 65.7 -16 -1.7 -5.6

TTCTGAAGCAGCTTCATTTG 1363 SEQ ID NO: 2587 -4.1 -21.9 66.1 -15.1 -2.1 -13.4

TGGAGAGAACGAAGTTTTGC 1549 SEQ ID NO: 2588 -4.1 -20.5 61.1 -14.6 -1.8 -8.6

GCTGTCCAAATTTCTCTGTC 1719 SEQ ID NO: 2589 -4.1 -24 71.4 -19.9 0 -4.5

TCCATCTGTGAGTTCAATCC 2136 SEQ ID NO: 2590 -4.1 -24.3 71.6 -20.2 0 -3.2

TCAAATCCCCCGCTGTATAA 2255 SEQ ID NO: 2591 -4.1 -25.5 68.2 -21.4 0 -3.1

GGCTGACACAGGTCCATTAG 2406 SEQ ID NO: 2592 -4.1 -25.6 73.8 -20.1 -1.3 -8.4

AGAACATATTTAAATGGCAA 2526 SEQ ID NO: 2593 -4.1 -16 51.1 -11.4 -0.1 -6.4

CCTCAGAACATATTTAAATG 2530 SEQ ID NO: 2594 -4.1 -17 53.3 -12.9 0 -6.4

TTGTAGTCATTTCCCTTAAT 2624 SEQ ID NO: 2595 -4.1 -21.9 65.9 -17.8 0 -2.3

AGAAATTTTTTATGAAATCC 2727 SEQ ID NO: 2596 -4.1 -15 49.5 -10.4 -0.1 -6

AATGTTGTATTTTTAAATGA 2801 SEQ ID NO: 2597 -4.1 -14.8 49.7 -10.7 0 -4.5

ACATGCGTCAATTTTGTTTC 2868 SEQ ID NO: 2598 -4.1 -21.2 63.8 -17.1 0 -5

CATAGATTAACATGCGTCAA 2877 SEQ ID NO: 2599 -4.1 -19.2 57.8 -15.1 0 -5

CATTTGAAGAATTTGCGATT 3119 SEQ ID NO: 2600 -4.1 -18.2 55.5 -14.1 0 -4.8

AAACACTATATCTTATTTGA 3267 SEQ ID NO: 2601 -4.1 -15.9 52 -11.8 0 -2.4

CCCCTCAGGACCTAAAGAAT 3289 SEQ ID NO: 2602 -4.1 -25.1 68 -20.5 -0.1 -4.8

AACATTAGTGACCTGCTGTA 19 SEQ ID NO: 2603 -4 -22.5 66.5 -18.5 0 -3.6

AGTTAAGAAAAAGCAAAGGA 100 SEQ ID NO: 2604 -4 -15 49 -11 0 -4.1

GACAAAGCTCTTCCAGATCT 483 SEQ ID NO: 2605 -4 -23.2 68 -19.2 0 -5.6

CCAGACACTTTATCTCCACA• 508 SEQ ID NO: 2606 -4 -24.5 70.2 -20.5 0 -2.6

CCCTGTCTCTCTTGTACATT 753 SEQ ID NO: 2607 -4 -26 76.1 -22 0 -6.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TGTTTGGTAACCTTGCAGGC 1004 SEQ ID NO: 2608 -4 -25.5 73.4 -20.6 -0.8 -6.7

TTAGCCTGCTCTTGCTGCAA 1219 SEQ ID NO: 2609 -4 -27.1 76.7 -20.8 -2.3 -9

AAGATACTACTCCTGGCCCA

1318 SEQ ID NO: 2610 -4 -26.5 73.1 -22.5 0 -6.6 ATAGTGGAGATCAGTTTAAA

2201 SEQ ID NO: 2611 -4 -18.1 57.5 -14.1 0 -5.4

ACATATTAATAGAATTTCCT 2502 SEQ ID NO: 2612 -4 -16.8 53.6 -12.8 0 -5.9

TGAAATCCAACAATGCCAAA 2715 SEQ ID NO: 2613 -4 -18.9 55.1 -14.9 0 -3

GTTGTATTTTTAAATGAACT 2798 SEQ ID NO: 2614 -4 -15.9 52.1 -11.4 -0.2 -4.7

ACCTTTTAAAATTGTGAAAT 3192 SEQ ID NO: 2615 -4 -15.5 50 -10.7 -0.6 -6.7

ACATTAGTGACCTGCTGTAA 18 SEQ ID NO: 2616 -3.9 -22.5 66.5 -18.6 0 ^• -3.6

GAAAAAAAATCCAGAATTCA 82 SEQ ID NO: 2617 -3.9 .-13.9 46.4 -10 0 -7.4

ACATCAGACTACAGTAACCC 128 SEQ ID NO: 2618 -3.9 -22.7 66.1 -18.8 0 -3.6

AGACACTTTATCTCCACACA

506 SEQ ID NO: 2619 -3.9 -22.7 67.1 -18.8 0 -2.5 CAGACACTTTATCTCCACAC

507 SEQ ID NO: 2620 -3.9 -22.7 67.1 -18.8 0 -2.6 ACGCTTTCTCTGTGTTTTGT

635 SEQ ID NO: 2621 -3.9 -24.4 73.2 -20.5 0 -3.3

GAGGGGGCATTGTCATGCTA 978 SEQ ID NO: 2622 -3.9 -26.7 77.1 -19.7 -3.1 -7.1

CTAGGAAAGTGGCCATATGT 1021 SEQ ID NO: 2623 -3.9 -22.8 66.3 -18.1 -0.3 -9

CCCATTATGGACTCGGGTGA 1081 SEQ ID NO: 2624 -3.9 -26.8 73.3 -22 -0.8 -6.8

GAAGATACTACTCCTGGCCC

1319 SEQ ID NO: 2625 -3.9 -26.4 73.3 -22.5 0 -6.6 ATTTGGTCATCAACCTTAAG

1348 SEQ ID NO: 2626 -3.9 -20.3 61.4 -14.7 -1.7 -5.6

GCATGCAACATTTCAATGAG 1837 SEQ ID NO: 2627 -3.9 -20.4 60.7 -15.5 -0.3 -9.8

GCCTAATTAATAAGATTAGT

2235 SEQ ID NO: 2628 -3.9 -17.4 54.8 -12.1 -1.3 -5.8 AGCCTAATTAATAAGATTAG

2236 SEQ ID NO: 2629 -3.9 -16.2 52.2 -11.2 -1 -5.8 AGCTTTACCATGGAGGAATC

2283 SEQ ID NO: 2630 -3.9 -22.8 66.9 -18 -0.6 -8.8

AGACACTCAAATTAGGCTGT 2456 SEQ ID NO: 2631 -3.9 -21.2 63.6 -17.3 10 -3.7

GGCAAGCTAACATATTAATA 2511 SEQ ID NO: 2632 -3.9 -18.1 55.8 -14.2 0 -5.6

TAACATCATGAACACGAGAC 2558 SEQ ID NO: 2633 -3.9 -18.2 55.4 -14.3 0 -6.4

TAGTCATTTCCCTTAATATT 2621 SEQ ID NO: 2634 -3.9 -20.4 62.2 -16.5 0 -4

CAATGCCAAAGCCACATTTC 2705 SEQ ID NO: 2635 -3.9 -23.1 64.7 -18.3 -0.7 -4.5

TTCAATTGCAGCAAGAATGA 2939 SEQ ID NO: 2636 -3.9 -19.4 58.5 -14.9 0 -8.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CACATGTAAAAATCACCATT 2981 SEQ ID NO: 2637 -3.9 -17.8 54.2 -13.9 0 -6.5

GAATTTGCGATTCTTTGTCC 3111 SEQ ID NO: 2638 -3.9 -22.5 66 -17.4 -1.1 -4.5

TTTGAAGAATTTGCGATTCT 3117 SEQ ID NO: 2639 -3.9 -18.8 57.4 -13.3 -1.6 -7.8

GTCATTTGAAGAATTTGCGA 3121 SEQ ID NO: 2640 -3.9 -19.7 59.3 -15.8 0 -4:8

CAAGACTTTCATACCTGTGG 3168 SEQ ID NO: 2641 -3.9 -22.2 65.4 -18.3 0 -3.2

GAATGTAAACACTATATCTT 3273 SEQ ID NO: 2642 -3.9 -16.2 52.4 -12.3 0 -4.2

CTGCCCCTCAGGACCTAAAG 3292 SEQ ID NO: 2643 -3.9 -27.9 74.5 -23.3 -0.4 -4.8

AGGTGAGGAGCCCATAATGG 531 SEQ ID NO: 2644 -3.8 -25.5 71.7 -20.9 -0.6 -5.5

TTAGACATTTTTGAAAACGA 666 SEQ ID NO: 2645 -3.8 -15.8 50.7 -12 0.6 -5.2

TACAGCTTCTAGCTTCATTC 692 SEQ ID NO: 2646 -3.8 -22.8 70.2 -17.2 -1.8 -6

TGCAGAGGAAATGGTCAGGT 860 SEQ ID NO: 2647 -3.8 -23.4 68.7 -19.1 -0.2 -4.9

ACTCAGACTTGATGGCCCGG 1041 SEQ ID NO: 2648 -3.8 -27.6 75 -23.1 -0.3 -8.3

TCACACTTCAAAAGTTCCAG 1159 SEQ ID NO: 2649 -3.8 -20.6 61.7 -15.9 -0.7 -4.2

AGAAGATACTACTCCTGGCC 1320 SEQ ID NO: 2650 -3.8 -24.4 70 -20.6 0 -6.2

AGGAAGAGGGAGGGGCTATT 2343 SEQ ID NO: 2651 -3.8 -24.8 72 -21 0 -3.7

AGAATGAACCTTGAGTCAAT 2926 SEQ ID NO: 2652 -3.8 -19.2 58.2 -14.9 0 -7.6

TGTTCAATTGCAGCAAGAAT 2941 SEQ ID NO: 2653 -3.8 -20 60.2 -15.5 0 -8.8

CTATATCTTATTTGACTTTA 3262 SEQ ID NO: 2654 -3.8 -17.2 55.9 -13.4 0 -2.4

AGGACCTAAAGAATGTAAAC 3283 SEQ ID NO: 2655 -3.8 -16.8 52.6 -13 0 -3.6

CCCTGGACTCTGTACTTTTT 41 SEQ ID NO: 2656 -3.7 -25.5 73.5 -21.8 0 -4.8

AAAAATCCAGAATTCATAAA

78 SEQ ID NO: 2657 -3.7 -13.7 46.2 -10 0 -7.4 AAAAAATCCAGAATTCATAA

79 SEQ ID NO: 2658 -3.7 -13.7 46.2 -10 0 -7.4 AAAAAAATCCAGAATTCATA

80 SEQ ID NO: 2659 -3.7 -13.7 46.2 -10 0 -7.4 CCGGCATCTGGCCCTGTTCC

414 SEQ ID NO: 2660 -3.7 -33.4 86.8 -27.4 -2.3 -6.6

CTTGTACATTGGCCCAAACT 743 SEQ ID NO: 2661 -3.7 -24.3 67.9 -20.6 0 -6.6

CTACTCCTGGCCCACTCGAC 1312 SEQ ID NO: 2662 -3.7 -29.8 79.5 -26.1 0 -6.6

CTTAAGTTCTCTGAAGAAGA 1334 SEQ ID NO: 2663 -3.7 -18.3 57.8 -13.1 -1.4 -6.3

CGAAGTTTTGCCACTAACTC 1540 SEQ ID NO: 2664 -3.7 -22.3 64.4 -17.9 -0.5 -3.7

ACCAGCTGGAAGTTTTCAAG 1633 SEQ ID NO: 2665 -3.7 -22.6 66.4 -16.6 -0.8 -12.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GATTTGGTGGAGCTACCACT 2432 SEQ ID NO: 2666 -3.7 -25.4 73.1 -17.9 -3.8 -12.5

GCTGTTCATGATTTGGTGGA 2441 SEQ ID NO: 2667 -3.7 -24.1 71.6 -20.4 0 -6.1

AGCTAACATATTAATAGAAT 2507 SEQ ID NO: 2668 -3.7 -15 49.7 -11.3 0 -5.9

CAAAGCCACATTTCAGCAAC 2699 SEQ ID NO: 2669 -3.7 -22 63.2 -17.5 -0.6 -4.1

CATCCTAGCAAAATGTGTTT 2821 SEQ ID NO: 2670 -3.7 -20.7 61.5' -17 0 -4.1

TTCTCTTTGCATAGATTAAC 2886 SEQ ID NO: 2671 -3.7 -19 59.8 -15.3 0 -3.7

GTTCAATTGCAGCAAGAATG 2940 SEQ ID NO: 2672 -3.7 -20 60.2 -15.6 0 -8.8

GTTAATAATACTGATAATAG 3140 SEQ ID NO: 2673 -3.7 -13.4 46.7 -9.7 0 -2.8

ATAACATTAAGGAAATTACC 3344 SEQ ID NO: 2674 -3.7 -15.4 49.9 -11.7 0 -3.2

CACATCAGACTACAGTAACC 129 SEQ ID NO: 2675 -3.6 -21.4 63.6 -17.8 0 -3.6

AAAGAAAAGTGCAGCTTGTC 172 SEQ ID NO: 2676 -3.6 -19.2 58.6 -14.6 -0.9 -7.6

AAAGCAGAAATCATTGAGCA 192 SEQ ID NO: 2677 -3.6 -18.6 56.6 -14 -0.9 -4.9

GTAAGTCCGTGCTTTAAAGA 280 SEQ ID NO: 2678 -3.6 -21.6 63.7 -17.4 -0.2 -8.1

CATGCGATCGAGCCAGTCCC 393 SEQ ID NO: 2679 -3.6 -29.8 78.5 -25.5 -0.1 -8.8

GCCCTGTCTCTCTTGTACAT 754 SEQ ID NO: 2680 -3.6 -27.7 80.4 -24.1 0 -6.3

AGAGTGGATGTTTTGAATTG

878 SEQ ID NO: 2681 -3.6 -19.1 59.7 -15.5 0 -3.1 ATTGACTTGTTCCTGGACAC

1658 SEQ ID NO: 2682 -3.6 -23.4 68.9 -19.1 -0.5 -6.2

AATTGTTTCAGTTCAGCTTT 2297 SEQ ID NO: 2683 -3.6 -21.2 65.9 -17.6 0 -4.5

CAGAACATATTTAAATGGCA 2527 SEQ ID NO: 2684 -3.6 -17.4 54 -13.8 0.8 -6.4

TGCATTTTCTTAACATCATG 2568 SEQ ID NO: 2685 -3.6 -19.2 59.3 -15.6 0 -4.7

CACACTTACATAAGATGAGG 2597 SEQ ID NO: 2686 -3.6 -18.8 57.7 -14.6 -0.3 -5

AATAAGGTCTAAGTTGCTTT 2670 SEQ ID NO: 2687 -3.6 -19.2 59.8 -15.6 0 -3.6

TAGTCATTTGAAGAATTTGC 3123 SEQ ID NO: 2688 -3.6 -18 57 -14.4 0 -3.9

ATATCTTATTTGACTTTAAA 3260 SEQ ID NO: 2689 -3.6 -15.2 50.8 -11.6 0 -4

GTTTTCCGGCATCTGGCCCT 419 SEQ ID NO: 2690 -3.5 -31.6 84.6 -25.8 -2.3 -6.6

CTTAGACATTTTTGAAAACG 667 SEQ ID NO: 2691 -3.5 -16.1 51.3 -12 -0.3 -5.2

CAGAGTGGATGTTTTGAATT

879 SEQ ID NO: 2692 -3.5 -19.8 61 -16.3 0 -3.1 CCGGCTAGGAAAGTGGCCAT

1025 SEQ ID NO: 2693 -3.5 -27.7 73.9 -22 -2.2 -9

TTAGCCTGGACTTGAGGCTC 1186 SEQ ID NO: 2694 -3.5 -26.4 76.4 -19.6 -3.3 -9.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GTTAGCCTGCTCTTGCTGCA 1220 SEQ ID NO: 2695 -3.5 -29 83 -23.2 -2.3 -7.2

AAGAAGATACTACTCCTGGC 1321 SEQ ID NO: 2696 -3.5 -21.7 64.2 -18.2 0 -4.3

CCAGTAACCAGGAAGATGGA 1447 SEQ ID NO: 2697 -3.5 -23.3 66 -18.7 -1 -4.5

CACCAAGAATTTCAGACATA 1589 SEQ ID NO: 2698 -3.5 -19.3 58.1 -15.8 0 -5:ι

CTAAATTTCTTCATAGTGGA 2213 SEQ ID NO: 2699 -3.5 -18.6 58.4 -15.1 0 -4.9

ATATTTAAATGGCAAGCTAA 2521 SEQ ID NO: 2700 -3.5 -16.9 53.2 -13.4 0 -6.4

GTAGTCATTTCCCTTAATAT

2622 SEQ ID NO: 2701 -3.5 -21.5 65 -18 0 -2.4 TGTAGTCATTTCCCTTAATA

2623 SEQ ID NO: 2702 -3.5 -21.5 64.9 -18 0 -2.3 ATAAGGTCTAAGTTGCTTTA

2669 SEQ ID NO: 2703 -3.5 -19.6 61.4 -16.1 0 -3.6

CCAAAGCCACATTTCAGCAA 2700 SEQ ID NO: 2704 -3.5 -23.8 66.1 -20.3 0.2 -4.1

AACAATGCCAAAGCCACATT 2707 SEQ ID NO: 2705 -3.5 -22.1 61.7 -17.7 -0.7 -4.4

TTGACATCCTAGCAAAATGT 2825 SEQ ID NO: 2706 -3.5 -20.2 60 -15.9 -0.6 -4.6

GGGAAGATTTGAATTACTTT 3016 SEQ ID NO: 2707 -3.5 -18.1 56.5 -14.6 0 -3.2

ATTAGTGACCTGCTGTAAAC 16 SEQ ID NO: 2708 -3.4 -21.1 63.1 -17.7 0 -3.6

TGTAAGTCCGTGCTTTAAAG 281 SEQ ID NO: 2709 -3.4 -21 62.3 -17.1 -0.2 -7.6

ATCTTCATCATAGGAGTAAT 467 SEQ ID NO: 2710 -3.4 -19.3 60.8 -15.9 0 -3.3

AGCTCTTCCAGATCTTCATC 478 SEQ ID NO: 2711 -3.4 -24.7 74.7 -21.3 0 -5.8

TAAGTCCATTGGCTCGGATG 798 SEQ ID NO: 2712 -3.4 -24.3 69.2 -20.2 -0.4 -6.6

TATGAATAGCCCATTATGGA 1090 SEQ ID NO: 2713 -3.4 -21.4 62.4 -17.1 -0.8 -5.6

GCCATTTTGCACATAAGCCC 1270 SEQ ID NO: 2714 -3.4 -27 73.5 -23.1 -0.1 -5

AGATACTACTCCTGGCCCAC 1317 SEQ ID NO: 2715 -3.4 -27.4 76 -24 0 -6.6

TTGTCGGTAAATGTGGTCGA 1406 SEQ ID NO: 2716 -3.4 -22.6 65.5 -18.6 -0.3 -4.8

CCGCTGTATAAGCCTAATTA 2246 SEQ ID NO: 2717 -3.4 -22.9 64.8 -17.9 -1.5 -6.1

TGGCAAGCTAACATATTAAT

2512 SEQ ID NO: 2718 -3.4 -18.4 56.3 -15 0 -5.5 ATGGCAAGCTAACATATTAA

2513 SEQ ID NO: 2719 -3.4 -18.4 56.3 -15 0 -5.5 CTCAGAACATATTTAAATGG

2529 SEQ ID NO: 2720 -3.4 -16.2 52 -12.3 -0.1 -6.4

GTGACTATTTGACATCCTAG 2833 SEQ ID NO: 2721 -3.4 -21.3 64.5 -17.9 0 -3.2

AAAAAAAATCCAGAATTCAT 81 SEQ ID NO: 2722 -3.3 -13.3 45.3 -10 0 -7.4

GTTAAGAAAAAGCAAAGGAA 99 SEQ ID NO: 2723 -3.3 -14.3 47.4 -11 0 -4.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TGAGCAAAAGAAAAGTGCAG 178 SEQ ID NO: 2724 -3.3 -17.2 53.3 -12.1 -1.8 -5.3

AAGCAGAAATCATTGAGCAA 191 SEQ ID NO: 2725 -3.3 -18.6 56.6 -14.3 -0.9 -4.9

TAAAGCAGAAATCATTGAGC 193 SEQ ID NO: 2726 -3.3 -17.6 54.8 -14.3 0 -4.5

CAGGTGAGGAGCCCATAATG 532 SEQ ID NO: 2727 -3.3 -25 70.3 -20.9 -0.6 -5.5

TAGACATTTTTGAAAACGAC 665 SEQ ID NO: 2728 -3.3 -15.9 50.9 -12 -0.3 -5.2

GAAGAAGATACTACTCCTGG 1322 SEQ ID NO: 2729 -3.3 -20.5 61.4 -17.2 0 -4

AAGAGCACCAAGAATTTCAG 1594 SEQ ID NO: 2730 -3.3 -19.8 59.3 -16.5 0 -5.1

CCAAATTTCTCTGTCTGCTG 1714 SEQ ID NO: 2731 -3.3 -23.3 68.3 -20 0 -4.5

TCGAAGAAGTAGCTGTCCAA 1730 SEQ ID NO: 2732 -3.3 -22.2 64.6 -18.4 -0.1 -5

ATTCACAGTTTGCAATACAA 2065 SEQ ID NO: 2733 -3.3 -19.2 58.8 -15.2 -0.3 -8.1

TGTAGGTACAGCTGATGCAT 2324 SEQ ID NO: 2734 -3.3 -23.7 70.5 -18.8 -1.6 -9.1

TAATTCACACTTACATAAGA 2602 SEQ ID NO: 2735 -3.3 -16.5 53 -12.7 -0.2 -5

TGTTGTATTTTTAAATGAAC 2799 SEQ ID NO: 2736 -3.3 -15 50.1 -11.2 -0.1 -4.6

TTTAAAATTGTGAAATAAGG 3188 SEQ ID NO: 2737 -3.3 -12.5 44.4 -8.3 -0.8 -6.3

TTAAACAAATGTTGATCCAC 3224 SEQ ID NO: 2738 -3.3 -17.1 53.3 -13.8 0.3 -6.4

CCCCTGCCCCTCAGGACCTA 3295 SEQ ID NO: 2739 -3.3 -35.3 88.5 -29.3 -2.7 -7.4

ACCATTTTAAATTGAGACAC 445 SEQ ID NO: 2740 -3.2 -17.9 55.4 -14.7 0 -5.4

TCTTCCAGATCTTCATCATA 475 SEQ ID NO: 2741 -3.2 -22.4 68.2 -18.2 -0.9 -5.8

AGGCTGCCGTGAGGGGGCAT 988 SEQ ID NO: 2742 -3.2 -31.6 84.9 -25.6 -2.8 -10.1

CCTTGCAGGCTGCCGTGAGG 994 SEQ ID NO: 2743 -3.2 -31 82.8 -25.9 -1.4 -11.6

AACCTTGCAGGCTGCCGTGA 996 SEQ ID NO: 2744 -3.2 -29.3 78.1 -24.5 -1.4 -10.1

GGTACTCAGACTTGATGGCC 1044 SEQ ID NO: 2745 -3.2 -25.7 74.5 -22 -0.1 -6.4

TGTCGGTAAATGTGGTCGAG 1405 SEQ ID NO: 2746 -3.2 -22.5 65.4 -18.6 -'0.5 -4.9

AATATACAAGAACCGTTCTG 2183 SEQ ID NO: 2747 -3.2 -18.4 55.7 -14.2 -0.9 -8.9

GTGTGGCTGACACAGGTCCA 2410 SEQ ID NO: 2748 -3.2 -28.2 80.6 -22.4 -2.6 -8.5

TCAGAACATATTTAAATGGC 2528 SEQ ID NO: 2749 -3.2 -17.1 54 -13.4 -0.1 -6.4

TTCACACTTACATAAGATGA 2599 SEQ ID NO: 2750 -3.2 -18.1 56.7 -14.2 -0.5 -5.9

ACCTAAAGAATGTAAACACT 3280 SEQ ID NO: 2751 -3.2 -16.8 52.4 -13.6 0 -4.2

CCTGCCCCTCAGGACCTAAA 3293 SEQ ID NO: 2752 -3.2 -29.9 77.4 -24.5 -2.2 -7.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ACACTTGCATGTTTTCCGGC 429 SEQ ID NO: 2753 -3.1 -26.3 73.9 -23.2 0 -6.5

ACGGGACAAAGCTCTTCCAG 487 SEQ ID NO: 2754 -3.1 -24.7 69 -20.5 -1 -6.8

CAATGAGAAGGTTATTATAG 1824 SEQ ID NO: 2755 -3.1 -16.2 52.7 -13.1 0 -2.1

AGGGGTTGTAACTTATGCTC 1862 SEQ ID NO: 2756 -3.1 -23.1 69.6 -20 0 -4 '.3

GCTGTTTGCAGGTCTAAGAC 2478 SEQ ID NO: 2757 -3.1 -24.1 72.2 -19.2 -1.8 -8.8

ACATAAGATGAGGGATACTG 2590 SEQ ID NO: 2758 -3.1 -18.9 58.1 -14.7 -1 -3.9

ACATCCTAGCAAAATGTGTT 2822 SEQ ID NO: 2759 -3.1 -20.8 61.7 -17.2 -0.2 -4.2

AAAGAATGTAAACACTATAT 3276 SEQ ID NO: 2760 -3.1 -13.4 46.1 -10.3 0 -4.2

GGACCTAAAGAATGTAAACA 3282 SEQ ID NO: 2761 -3.1 -17.5 53.7 -14.4 0 -3.9

TGCCCCTCAGGACCTAAAGA 3291 SEQ ID NO: 2762 -3.1 -27.6 73.9 -24 . -0.2 -4.8

CCCCCTGCCCCTCAGGACCT 3296 SEQ ID NO: 2763 -3.1 -37.6 92 -31.8 -2.7 -7.2

CCTTAGTGAAAGTTAAGAAA 110 SEQ ID NO: 2764 -3 -16.6 52.7 -13.1 -0.2 -4.8

TAAGTCCGTGCTTTAAAGAC 279 SEQ ID NO: 2765 -3 -20.6 61.2 -17 -0.2 -8.1

CCCATAATGGTACCCAGACA 521 SEQ ID NO: 2766 -3 -26.2 70.7 -22.3 -0.7 -7.8

GCTTTCTCTGTGTTTTGTCA 633 SEQ ID NO: 2767 -3 -24.5 75.8 -21.5 0 -2.8

AGGTCAGAGGGCATAGCTTG 844 SEQ ID NO: 2768 -3 -25.5 75.6 -21.8 -0.4 -4.7

TAGCCTGGACTTGAGGCTCA 1185 SEQ ID NO: 2769 -3 -27 77.1 -20.7 -3.3 -9.2

TAAGTTCTCTGAAGAAGATA 1332 SEQ ID NO: 2770 -3 -17 54.9 -12.5 -1.4 -4.9

GGTCATCAACCTTAAGTTCT 1344 SEQ ID NO: 2771 -3 -22.7 67.8 -18.6 -1 -5.6

GTAAATGTGGTCGAGGATTA 1400 SEQ ID NO: 2772 -3 -20.5 61.7 -17.5 0 -4.9

GTCGGTAAATGTGGTCGAGG 1404 SEQ ID NO: 2773 -3 -23.7 68.1 -20 -0.5 -4.9

CAGTTTGCAATACAAATACC 2060 SEQ ID NO: 2774 -3 -19 57.3 -14.3 -1.7 -8.1

TTCCTATTAGCTGTTTGCAG 2487 SEQ ID NO: 2775 -3 -23.5 70.4 -18.9 -1.5 -7

AACATGCGTCAATTTTGTTT 2869 SEQ ID NO: 27-76 -3 -20.1 60.3 -17.1 0 -5.6

GTATTAATACTTTATTTTAA 3240 SEQ ID NO: 2777 -3 -14 48.4 -10.3 0 -9

CCCTGCCCCTCAGGACCTAA 3294 SEQ ID NO: 2778 -3 -32.6 82.9 -26.9 -2.7 -7.4

GACACATCAGACTACAGTAA 131 SEQ ID NO: 2779 -2.9 -20 61.1 -17.1 0 -3.6

CTCTTCCAGATCTTCATCAT-

476 SEQ ID NO: 2780 -2.9 -23.6 70.9 -19.7 -0.9 -5.8 GCTCTTCCAGATCTTCATCA

477 SEQ ID NO: 2781 -2.9 -25.4 75.6 -21.5 -0.9 -5.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AGGGCCCTGTCTCTCTTGTA 757 SEQ ID NO: 2782 -2.9 -29.2 84.7 -24.6 0 -11.5

AGGAAGATGGATCCTTCCTT 1438 SEQ ID NO: 2783 -2.9 -24.3 70 -17.9 -3.5 -12.4

AAGGAAGAGGGAGGGGCTAT 2344 SEQ ID NO: 2784 -2.9 -24 69.2 -21.1 0 -3.7

GAAAGTTTGTAGTCATTTCC 2630 SEQ ID NO: 2785 -2.9 -20.4 63.2 -17 -0.2 -4.5

ATTTGAAGAATTTGCGATTC 3118 SEQ ID NO: 2786 -2.9 -17.9 55. ≤ -13.8 -1.1 -4.8

TTAAAATTGTGAAATAAGGC 3187 SEQ ID NO: 2787 -2.9 -14.2 47.6 -10.7 -0.3 -3.8

CACAGATCCCCCTGCCCCTC

3303 SEQ ID NO: 2788 -2.9 -34.6 87.5 -31 -0.4 -4.5 TCACAGATCCCCCTGCCCCT

3304 SEQ ID NO: 2789 -2.9 -34.6 87.5 -31 -0.4 -3.7 AGCAGAAATCATTGAGCAAA

190 SEQ ID NO: 2790 -2.8 -18.6 56.6 -14.8 -0.9 -4.9

CCCAGACACTTTATCTCCAC 509 SEQ ID NO: 2791 -2.8 -25.8 72.6 -23 0 -2.6

GGTACCCAGACACTTTATCT 513 SEQ ID NO: 2792 -2.8 -24.8 71.6 -22 0 -6.8

GAGCCCATAATGGTACCCAG 524 SEQ ID NO: 2793 -2.8 -27.1 73.3 -23.4 -0.7 -7.8

TGGATGTTTTGAATTGCAGA 874 SEQ ID NO: 2794 -2.8 -20.4 61.8 -17.6 0 -5.3

GGCCTTTGGAGGCAGAGTGG 891 SEQ ID NO: 2795 -2.8 -28.6 81 -21.4 -4.4 -9.9

GGTTAGCCTGCTCTTGCTGC 1221 SEQ ID NO: 2796 -2.8 -29.5 84.8 -24.7 -2 -7.1

TAAATGTGGTCGAGGATTAA 1399 SEQ ID NO: 2797 -2.8 -18.6 56.8 -15.8 0 -4.9

TTGATCAAACTGGAGAGAAC 1559 SEQ ID NO: 2798 -2.8 -18 55.9 -14.5 0 -9.1

GCACCAAGAATTTCAGACAT 1590 SEQ ID NO: 2799 -2.8 -21.4 62.6 -18.6 0 -5.1

ACATTTCAATGAGAAGGTTA 1830 SEQ ID NO: 2800 -2.8 -18.2 57.1 -14.8 -0.3 -5.8

GAGTACTTTTTTTCTTCCTG 1939 SEQ ID NO: 2801 -2.8 -21.9 67.5 -19.1 0 -6.4

TCAATCCACTCCATTACAAT 2123 SEQ ID NO: 2802 -2.8 -21.7 63 -18.9 0 -1.7

CTGTGAGTTCAATCCACTCC 2131 SEQ ID NO: 2803 -2.8 -25 72.6 -20.9 -1.2 -4.6

TAGTGGAGATCAGTTTAAAT 2200 SEQ ID NO: 2804 -2.8 -18.1 57.5 -15.3 0 -5.4

ATAAGCCTAATTAATAAGAT 2239 SEQ ID NO: 2805 -2.8 -15.4 50.1 -12.6 '0 -4.7

CTGCATTTTCTTAACATCAT 2569 SEQ ID NO: 2806 -2.8 -20.1 61.4 -17.3 0 -4.9

CAACAATGCCAAAGCCACAT 2708 SEQ ID NO: 2807 -2.8 -22.7 62.5 -19 -0.7 -3.7

AATAGTCATTTGAAGAATTT 3125 SEQ ID NO: 2808 -2.8 -15.5 51.2 -12.7 0 -3.4

GTTAAAAATAATTACCAATC 3370 SEQ ID NO: 2809 -2.8 -13.6 46.3 -10.8 0 -4.4

AAGTTAAGAAAAAGCAAAGG 101 SEQ ID NO: 2810 -2.7 -13.7 46.4 -11 0 -4.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ATGCGATCGAGCCAGTCCCA 392 SEQ ID NO: 2811 -2.7 -29.8 78.5 -26.4 -0.1 -8.8

GTCTGGTAACTATCCATATA 1108 SEQ ID NO: 2812 -2.7 -21.2 64.4 -17.8 -0.4 -3.6

AATAGGCCATGATTTTAGCC 1200 SEQ ID NO: 2813 -2.7 -23.1 66.7 -19.1 -1.2 -7.7

AAATGTGGTCGAGGATTAAG 1398 SEQ ID NO: 2814 -2.7 -18.9 57.5 -16.2 0 -4:9

TGATCAAACTGGAGAGAACG 1558 SEQ ID NO: 2815 -2.7 -18.7 56.3 -16 0 -6

TCACACTTACATAAGATGAG 2598 SEQ ID NO: 2816 -2.7 -18 56.5 -14.6 -0.4 -5.7

TTTGTAGTCATTTCCCTTAA 2625 SEQ ID NO: 2817 -2.7 -22 66.3 -19.3 0 -2

ATCCTAGCAAAATGTGTTTA 2820 SEQ ID NO: 2818 -2.7 -19.7 59.8 -17 0 -4.1

ATGTTCAATTGCAGCAAGAA 2942 SEQ ID NO: 2819 -2.7 -20 60.2 -16.6 0 -8.8

GGCAAGACTTTCATACCTGT 3170 SEQ ID NO: 2820 -2.7 -24 ^' 69.7 -21.3 0 -4

TTTCCGGCATCTGGCCCTGT 417 SEQ ID NO: 2821 -2.6 -31.5 84 -27.1 -1.8 -6.6

TCTTCATCATAGGAGTAATT 466 SEQ ID NO: 2822 -2.6 -19.4 61.2 -16.8 0 -3.3

ACAAAGCTCTTCCAGATCTT 482 SEQ ID NO: 2823 -2.6 -22.7 67 -20.1 3 -5.8

CTCAGACTTGATGGCCCGGC 1040 SEQ ID NO: 2824 -2.6 -29.2 78.6 -25.9 -0.3 -8.3

AGCTGTTTGCAGGTCTAAGA 2479 SEQ ID NO: 2825 -2.6 -23.9 71.9 -19.5 -1.8 -6

TATCTGAATTAGAAGACATT 243 SEQ ID NO: 2826 -2.5 -16.2 52.7 -13.1 -0.3 -3.9

CGACCGCGGGCGGGGATGGG 337 SEQ ID NO: 2827 -2.5 -32.6 79.4 -27.8 -1.9 -12.4

TCCAGATCTTCATCATAGGA

472 SEQ ID NO: 2828 -2.5 -22.8 68.5 -19.3 -0.9 -5.8 TTCCAGATCTTCATCATAGG

473 SEQ ID NO: 2829 -2.5 -22.3 67.5 -19.3 -0.1 -5.8 GCTCTTGCTGCAAATAGGCC

1212 SEQ ID NO: 2830 -2.5 -26.6 74.6 -23.2 -0.5 -9.3

CCCACTCGACAATGGAGAAG 1302 SEQ ID NO: 2831 -2.5 -23.5 65 -20.2 -0.6 -5.8

ATCCCCCGCTGTATAAGCCT 2251 SEQ ID NO: 2832 -2.5 -30.5 79.1 -26.4 -1.5 -5.7

CCCTCAGGACCTAAAGAATG 3288 SEQ ID NO: 2833 -2.5 -23.1 64.6 -20.6 0 -4.8

GATCGAGCCAGTCCCAGGGC 388 SEQ ID NO: 2834 -2.4 -31.4 84.5 -27.4 -1.5 -7.7

AAGCTCTTCCAGATCTTCAT 479 SEQ ID NO: 2835 -2.4 -23.6 70.4 -21.2 0.2 -5.8

CTCTGGGGCTGTGAAGCTTT 2086 SEQ ID NO: 2836 -2.4 -26.5 76.5 -20.8 -3.3 -9.4

CGCTGTATAAGCCTAATTAA 2245 SEQ ID NO: 2837 -2.4 -20.2 59.3 -16.2 -1.5 -7.5

CCCGCTGTATAAGCCTAATT ■ 2247 SEQ ID NO: 2838 -2.4 -25.2 68.7 -21.2 -1.5 -5.7

GACCACAGGGCAGAGGTGCT 2374 SEQ ID NO: 2839 -2.4 -29 81.1 -24.3 -2.3 -7.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ATTAGCTGTTTGCAGGTCTA

2482 SEQ ID NO: 2840 -2.4 -23.8 72.4 -19.8 -1.5 -7.1 GAAATCCAACAATGCCAAAG

2714 SEQ ID NO: 2841 -2.4 -18.9 55.2 -16.5 0 -3

CTACAGCAGACTTTGGTCTA 3078 SEQ ID NO: 2842 -2.4 -23.3 70 -18.6 -2.3 -7.4

TCCAGAATTCATAAAGTTAC 73 SEQ ID NO: 2843 -2.3 -17.7 55.6 -15.4 0 -7.4

ACACATCAGACTACAGTAAC 130 SEQ ID NO: 2844 -2.3 -19.6 60.3 -17.3 0 -3.6

TGCGATCGAGCCAGTCCCAG 391 SEQ ID NO: 2845 -2.3 -29.8 78.8 -26.8 -0.1 -8.8

CTTCATCATAGGAGTAATTC 465 SEQ ID NO: 2846 -2.3 -19.4 61.2 -17.1 0 -2.9

TATACAAGAACCGTTCTGTC 2181 SEQ ID NO: 2847 -2.3 -20.7 61.7 -17.4 -0.9 -8.9

TTAACATCATGAACACGAGA 2559 SEQ ID NO: 2848 -2.3 -18.1 55.2 -15.8 0 -6.9

CTTTCCAGGACACATGTAAA 2991 SEQ ID NO: 2849 -2.3 -21.3 62.7 -19 0 -6.5

TACTTTTTCCAACATTAGTG 29 SEQ ID NO: 2850 -2.2 -19.5 60.1 -17.3 0 -2.9

AATCCCCAGTATCTGAATTA 252 SEQ ID NO: 2851 -2.2 -22.3 64.5 -19.5 -0.3 -4.1

CAACACTTAGACATTTTTGA 672 SEQ ID NO: 2852 -2.2 -18.3 56.9 -15.5 -0.3 -2.7

TGAAGCAGCTTCATTTGGTC 1360 SEQ ID NO: 2853 -2.2 -23.3 69.8 -18.5 -2 -13.2

AACATTTCAATGAGAAGGTT

1831 SEQ ID NO: 2854 -2.2 -17.8 55.7 -15 -0.3 -6.2 CAACATTTCAATGAGAAGGT

1832 SEQ ID NO: 2855 -2.2 -18.4 56.6 -15.6 -0.3 -5.8 ATTAGCGTTACTTGGAGCAG

1963 SEQ ID NO: 2856 -2.2 -22.9 67.7 -19.8 -0.7 -4.1

TCCCCCGCTGTATAAGCCTA 2250 SEQ ID NO: 2857 -2.2 -30.2 78.6 -26.4 -1.5 -5.7

TGACCACAGGGCAGAGGTGC 2375 SEQ ID NO: 2858 -2.2 -28.1 78.9 -24.3 -1.5 -6.7

ATTTGGTGGAGCTACCACTG 2431 SEQ ID NO: 2859 -2.2 -24.8 71.6 -19.6 -3 -11.7

TATTAGCTGTTTGCAGGTCT

2483 SEQ ID NO: 2860 -2.2 -23.8 72.4 -19.8 -1.8 -7.1 TGCCTGCATTTTCTTAACAT

2572 SEQ ID NO: 2861 -2.2 -22.8 66.5 -20.6 0 -5.2

CAGAAATAAGGTCTAAGTTG 2674 SEQ ID NO: 2862 -2.2 -16.9 54 -14.7 0 -2.7

TCCTAGCAAAATGTGTTTAA 2819 SEQ ID NO: 2863 -2.2 -19 57.9 -16.8 10 -3.8

AACACTATATCTTATTTGAC 3266 SEQ ID NO: 2864 -2.2 -16.8 54.3 -14.6 0 -2.4

AAAAATAACATTAAGGAAAT 3348 SEQ ID NO: 2865 -2.2 -10.6 40.6 -8.4 0 -2.9

TTAGTGACCTGCTGTAAACC 15 SEQ ID NO: 2866 -2.1 -23.1 66.8 -21 0 -3.6

ATCTGAATTAGAAGACATTC 242 SEQ ID NO: 2867 -2.1 -16.9 54.5 -14.2 -0.3 -4.6

TTCCGGCATCTGGCCCTGTT 416 SEQ ID NO: 2868 -2.1 -31.5 84 -27.1 -2.3 -6.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CTTGGATCACCTGAGACATG 828 SEQ ID NO: 2869 -2.1 -23.1 67.1 -20 -0.9 -5.9

CAGGCTGCCGTGAGGGGGCA 989 SEQ ID NO: 2870 -2.1 -32.3 85.9 -27.4 -2.8 -10.1

GCTAGGAAAGTGGCCATATG 1022 SEQ ID NO: 2871 -2.1 -23.4 67.3 -20.5 -0.3 -9

CTCGTCTGGTAACTATCCAT 1111 SEQ ID NO: 2872 -2.1 -23.9 69.3 -21.1 -0.4 -3:7

GATACTACTCCTGGCCCACT 1316 SEQ ID NO: 2873 -2.1 -28.3 77.6 -26.2 0 -6.6

CTAAAGAGCACCAAGAATTT

1597 SEQ ID NO: 2874 -2.1 -18.6 56.2 -16.5 0 -4.1 AGGGCAGAGGTGCTCGGGCC

2368 SEQ ID NO: 2875 -2.1 -32 87.5 -27.1 -2.8 -11

GCAAGCTAACATATTAATAG 2510 SEQ ID NO: 2876 -2.1 -16.9 53.5 -14.8 0 -5.9

TATTTAAATGGCAAGCTAAC 2520 SEQ ID NO: 2877 -2.1 -17.1 53.6 -15 0 -6.4

CTGCCTGCATTTTCTTAACA 2573 SEQ ID NO: 2878 -2.1 -23.7 68.5 -21.6 . 0 -5.4

ACTTACATAAGATGAGGGAT 2594 SEQ ID NO: 2879 -2.1 -19 58.5 -16.4 -0.2 -5

TTTGCTTTGAAAGTTTGTAG 2638 SEQ ID NO: 2880 -2.1 -18.6 58.7 -16.5 0 -4.5

AAATAAGGTCTAAGTTGCTT 2671 SEQ ID NO: 2881 -2.1 -18.4 57.5 -16.3 0 -3.6

CGAGCCAGTCCCAGGGCTTC 385 SEQ ID NO: 2882 -2 -31.8 85.6 -27 -2.8 -7.8

AAAGCTCTTCCAGATCTTCA 480 SEQ ID NO: 2883 -2 -22.9 68 -20.9 0.2 -5.8

TCACAGGTGAGGAGCCCATA 535 SEQ ID NO: 2884 -2 -27 76.2 -24.4 -0.3 -6.5

CCCGGCTAGGAAAGTGGCCA 1026 SEQ ID NO: 2885 -2 -29.7 77.1 -25.5 -2.2 -9

ACTAAAGAGCACCAAGAATT

1598 SEQ ID NO: 2886 -2 -18.7 56.4 -16.7 0 -4.1 GCAGTTCAGAGTACTTTTTT

1947 SEQ ID NO: 2887 -2 -22 68.6 -20 0 -6.4

CAAATCCCCCGCTGTATAAG 2254 SEQ ID NO: 2888 -2 -25.1 67.1 -23.1 0 -3.1

TTGTTTCAGTTCAGCTTTAC 2295 SEQ ID NO: 2889 -2 -21.8 68.4 -19.8 0 -4.5

AAGCTAACATATTAATAGAA 2508 SEQ ID NO: 2890 -2 -14.3 48.1 -12.3 0 -5.9

AGGCAAGACTTTCATACCTG 3171 SEQ ID NO: 2891 -2 -22.8 66.7 -20.8 0 -4

ATCACAGATCCCCCTGCCCC 3305 SEQ ID NO: 2892 -2 -33.7 85.6 -31 -0.4 -4.5

TGAATTAGAAGACATTCTTA 239 SEQ ID NO: 2893 -1.9 -16.3 53 -13 -1.3 -6.2

GAATTGCAGAGGAAATGGTC 864 SEQ ID NO: 2894 -1.9 -20.3 61 -18.4 0 -5.2

GCCTTTGGAGGCAGAGTGGA 890 SEQ ID NO: 2895 -1.9 -28 79.7 -22.5 -3.6 -9.3

AAAGAGCACCAAGAATTTCA- 1595 SEQ ID NO: 2896 -1.9 -19.1 57.3 -17.2 0 -5.1

TTGCTTTGAAAGTTTGTAGT 2637 SEQ ID NO: 2897 -1.9 -19.7 61.5 -17.8 0 -4.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTTCCAGGACACATGTAAAA 2990 SEQ ID NO: 2898 -1.9 -19.7 58.9 -17.8 0 -6.5

AAAAGAAAAGTGCAGCTTGT 173 SEQ ID NO: 2899 -1.8 -18.1 55.5 -15.6 -0.4 -7.1

GCAGAAATCATTGAGCAAAA 189 SEQ ID NO: 2900 -1.8 -17.9 54.7 -15.6 -0.1 -4.5

AAGTTCTCTGAAGAAGATAC 1331 SEQ ID NO: 2901 -1.8 -17.5 56 -14.2 -1.4 -4.9

AGGATTAAGAGCTCACTCCA 1387 SEQ ID NO: 2902 -1.8 -23.5 69.1 -20.2 -1.4 -9.3

TGTGGTCGAGGATTAAGAGC 1395 SEQ ID NO: 2903 -1.8 -22.7 67.3 -20.9 0 -4.4

ATTTCAATGAGAAGGTTATT 1828 SEQ ID NO: 2904 -1.8 -17.4 55.6 -15 -0.3 -5

AAATATACAAGAACCGTTCT 2184 SEQ ID NO: 2905 -1.8 -17.7 54.1 -15 -0.7 -8.6

AAAGTATTAATACTTTATTT 3243 SEQ ID NO: 2906 -1.8 -13.5 47.1 -8.5 -2.1 -14.4

GGATCCGTGTCGGTCCGGAA 317 SEQ ID NO: 2907 -1.7 .-29.3 77.2 -24.3 -3.3 -11.4

CAAAGCTCTTCCAGATCTTC 481 SEQ ID NO: 2908 -1.7 -22.9 68 -21.2 2.8 -5.8

AGGAAATGGTCAGGTCAGAG 855 SEQ ID NO: 2909 -1.7 -22 66.3 -19.8 -0.2 -3.2

GCAGAGTGGATGTTTTGAAT 880 SEQ ID NO: 2910 -1.7 -21.5 65 -19.8 0 -3.4

CATTATGGACTCGGGTGAGC 1079 SEQ ID NO: 2911 -1.7 -24.6 70.7 -21.5 -1.3 -5.6

TAAAGAGCACCAAGAATTTC 1596 SEQ ID NO: 2912 -1.7 -18.1 55.6 -16.4 0 -4.1

TTATAGGGCACATCCCCGTT 1810 SEQ ID NO: 2913 -1.7 -27.8 75.5 -24.8 -1.2 -6.9

GATTCGGTGACCACAGGGCA 2382 SEQ ID NO: 2914 -1.7 -27.6 75.9 -25.1 -0.6 -8.2

GGATACTGCCTGCATTTTCT ^' 2578 SEQ ID NO: 2915 -1.7 -25.4 73.2 -23.7 0 -5.4

GGGATACTGCCTGCATTTTC 2579 SEQ ID NO: 2916 -1.7 -25.7 73.8 -23.1 -0.7 -6.7

GTTTGTAGTCATTTCCCTTA

2626 SEQ ID NO: 2917 -1.7 -23.9 72.2 -22.2 0 -1.9

CAGCAAGAATGAACCTTGAG 2931 SEQ ID NO: 2918 -1.7 -20.1 59.3 -16.9 -1.4 -5.1

CAGGACACATGTAAAAATCA 2986 SEQ ID NO: 2919 -1.7 -17.5 ^' 54.1 -15.8 0 -6.5

CCACATCTGCACAGCTACCT 3208 SEQ ID NO: 2920 -1.7 -27.8 76.7 -25.5 -0.3 -4.8

TTGGCTTAAAGCAGAAATCA 199 SEQ ID NO: 2921 -1.6 -19.2 58 -15.6 V2 -7.3

GCAGTTCTTTGGCTTAAAGC 207 SEQ ID NO: 2922 -1.6 -23.4 69.6 -20.6 -1.1 -6.2

TCTGAATTAGAAGACATTCT 241 SEQ ID NO: 2923 -1.6 -17.8 56.4 -15 -1.1 -6.2

TGGTAACCTTGCAGGCTGCC

1000 SEQ ID NO: 2924 -1.6 -28.8 79.1 -25.7 -1.4 -8.8 TTGGTAACCTTGCAGGCTGC

1001 SEQ ID NO: 2925 -1.6 -26.9 75.9 -24.2 -1 -7.2 CGAGGATTAAGAGCTCACTC

1389 SEQ ID NO: 2926 -1.6 -22.2 65.6 -19.4 -1 -9.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GACACCTTCTACCAGCTGGA 1643 SEQ ID NO: 2927 -1.6 -27.1 75.9 -23.2 0 -12.7

CCCCCGCTGTATAAGCCTAA 2249 SEQ ID NO: 2928 -1.6 -29.1 74.8 -26.4 -1 -5.2

GAGGGATACTGCCTGCATTT

2581 SEQ ID NO: 2929 -1.6 -25.8 73.4 -23.3 -0.7 -6.7 CACTTACATAAGATGAGGGA

2595 SEQ ID NO: 2930 -1.6 -19.7 59.8 -17.5 -0.3 -5 AAACTTGGATGATGAAAAAG

2776 SEQ ID NO: 2931 -1.6 -14 46.9 -12.4 0 -2.9

ATAGTCATTTGAAGAATTTG 3124 SEQ ID NO: 2932 -1.6 -16.2 52.9 -14.6 0 -3.9

TGGCTTAAAGCAGAAATCAT 198 SEQ ID NO: 2933 -1.5 -19.1 57.7 -15.6 -2 -7.3

GTACCCAGACACTTTATCTC 512 SEQ ID NO: 2934 -1.5 -24 70.6 -22.5 0 -3.2

GAGGAAATGGTCAGGTCAGA 856 SEQ ID NO: 2935 -1.5 -22.6 67.4 -20.6 -0.2 -3.2

TGCTCTTGCTGCAAATAGGC 1213 SEQ ID NO: 2936 -1.5 -24.6 70.8 -21.8 -1.2 -9.1

AGTGGAGATCAGTTTAAATA 2199 SEQ ID NO: 2937 -1.5 -18.1 57.5 -16.6 0 -5.4

ACTGCCTGCATTTTCTTAAC 2574 SEQ ID NO: 2938 -1.5 -23.2 67.9 -21.7 0 -5.4

TGAGGGATACTGCCTGCATT

2582 SEQ ID NO: 2939 -1.5 -25.7 72.9 -23.3 -0.7 -6.7 ACACTTACATAAGATGAGGG

2596 SEQ ID NO: 2940 -1.5 -19.3 59 -17.2 -0.3 -5 ATTTGCTTTGAAAGTTTGTA

2639 SEQ ID NO: 2941 -1.5 -18.6 58.5 -17.1 0 -4.5

GTATCACTCTCTTCCTTTCC 3042 SEQ ID NO: 2942 -1.5 -25.7 76.9 -24.2 0 -1.6

TACTGATAATAGTCATTTGA 3132 SEQ ID NO: 2943 -1.5 -17.2 55.4 -15.2 -0.2 -4.1

TCCGGCATCTGGCCCTGTTC 415 SEQ ID NO: 2944 -1.4 -31.8 85.4 -28.1 -2.3 -6.6

GCAGAGGAAATGGTCAGGTC 859 SEQ ID NO: 2945 -1.4 -23.8 70.5 -21.9 -0.2 -3.6

AGACTTGATGGCCCGGCTAG 1037 SEQ ID NO: 2946 -1.4 -27.8 75.6 -25.7 -0.4 -8.1

CCTGCTCTTGCTGCAAATAG 1215 SEQ ID NO: 2947 -1.4 -24.5 69.6 -21.8 -1.2 -9.3

GTGCTTGCTTCGGTTAGCCT 1232 SEQ ID NO: 2948 -1.4 -28.9 81.8 -26.6 -0.7 -5.2

TTAATTCACACTTACATAAG 2603 SEQ ID NO: 2949 -1.4 -16 52.1 -14.6 0 -4.5

TTGAAGAATTTGCGATTCTT 3116 SEQ ID NO: 2950 -1.4 -18.8 57.4 -14.2 -3.2 -9.3

CTTTAAAGTATTAATACTTT 3247 SEQ ID NO: 2951 -1.4 -14.4 49 -9.7 -2.2 -14.6

GCCCCTCAGGACCTAAAGAA 3290 SEQ ID NO: 2952 -1.4 -26.9 71.9 -25 -0.2 -4.8

GGACACATCAGACTACAGTA 132 SEQ ID NO: 2953 -1.3 -21.9 65.9 -19.9 -0.4 -4

TTAAAGCAGAAATCATTGAG 194 SEQ ID NO: 2954 -1.3 -15.9 51.4 -14.6 0 -4.5

GGCAGTTCTTTGGCTTAAAG 208 SEQ ID NO: 2955 -1.3 -22.8 67.9 -20.5 -0.9 -5.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CACCATTTTAAATTGAGACA 446 SEQ ID NO: 2956 -1.3 -18.4 56.1 -17.1 0 -5.4

TGAGGAGCCCATAATGGTAC 528 SEQ ID NO: 2957 -1.3 -24.2 68.9 -22 -0.7 -5.5

GAGGCAGAGTGGATGTTTTG 883 SEQ ID NO: 2958 -1.3 -23.4 70.3 -22.1 0 -4

ACTATCCATATATGAATAGC 1100 SEQ ID NO: 2959 -1.3 -18.7 57.8 -16.9 0 -7.5

CCTTAAGTTCTCTGAAGAAG 1335 SEQ ID NO: 2960 -1.3 -19.7 60.3 -16.9 -1.4 -7.7

ATTCGGTGACCACAGGGCAG 2381 SEQ ID NO: 2961 -1.3 -27 74.9 -24.8 -0.8 -8.2

CCAGGACACATGTAAAAATC 2987 SEQ ID NO: 2962 -1.3 -18.8 56.4 -17.5 0 -6.5

CTTAAAGCAGAAATCATTGA 195 SEQ ID NO: 2963 -1.2 -16.8 53 -15.6 0 -4.2

TCAGACTTGATGGCCCGGCT 1039 SEQ ID NO: 2964 -1.2 -29.2 78.6 -27.3 -0.5 -8.3

GCTCGTCTGGTAACTATCCA 1112 SEQ ID NO: 2965 -1.2 -25.7 73.6 -23.9 -0.3 -3.5

AACTAAAGAGCACCAAGAAT 1599 SEQ ID NO: 2966 -1.2 -17.9 54.3 -16.7 0 -4.1

ACATCTAAACTAAAGAGCAC 1606 SEQ ID NO: 2967 -1.2 -17.2 54 -16 0 -4.1

GGAGCAGTTCAGAGTACTTT

1950 SEQ ID NO: 2968 -1.2 -23.5 72 -21.8 -0.2 -6.6 GCTGTATAAGCCTAATTAAT

2244 SEQ ID NO: 2969 -1.2 -19.4 58.8 -17.1 -1 -7.3

TTAGCTGTTTGCAGGTCTAA 2481 SEQ ID NO: 2970 -1.2 -23.1 69.9 -20.1 -1.8 -7.1

TACTGCCTGCATTTTCTTAA 2575 SEQ ID NO: 2971 -1.2 -22.7 66.7 -21.5 0 -5.4

CATGCGTCAATTTTGTTTCC 2867 SEQ ID NO: 2972 -1.2 -23 67 -21.8 0 -4.6

ACACATGTAAAAATCACCAT 2982 SEQ ID NO: 2973 -1.2 -17.9 54.4 -16.7 0 -6.5

GAAGAATTTGCGATTCTTTG 3114 SEQ ID NO: 2974 -1.2 -18.8 57.4 -14.2 -3.4 -8.6

GGAAAAAAAATCCAGAATTC 83 SEQ ID NO: 2975 -1.1 -14.4 47.4 -12.4 -0.7 -6.8

TTGCAGGCTGCCGTGAGGGG 992 SEQ ID NO: 2976 -1.1 -30.5 82.6 -27.8 -1.5 -9.3

GGACACCTTCTACCAGCTGG 1644 SEQ ID NO: 2977 -1.1 -27.7 77.1 -24.6 0 -12.2

CATTTCAATGAGAAGGTTAT 1829 SEQ ID NO: 2978 -1.1 -18 56.5 -16.3 -0.3 -4.4

CATGCAACATTTCAATGAGA 1836 SEQ ID NO: 2979 -1.1 -19.2 58.1 -17.5 -0.3 -7.1

CAGTTCAGAGTACTTTTTTT 1946 SEQ ID NO: 2980 -1.1 -20.3 64.3 -19.2 0 -6.4

TGGAGCAGTTCAGAGTACTT

1951 SEQ ID NO: 2981 -1.1 -23.4 71.5 -21.8 -0.2 -6.6 GACCGTGTTGGTATCCATCT

2149 SEQ ID NO: 2982 -1.1 -26.6 75.3 -23.9 -1.5 -5.1

CAGCTTTACCATGGAGGAAT 2284 SEQ ID NO: 2983 -1.1 -23.1 66.6 -21.1 -0.6 -8.8

AGATTCGGTGACCACAGGGC 2383 SEQ ID NO: 2984 -1.1 -26.9 75.1 -25.1 -0.4 -6.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

AGTTTGTAGTCATTTCCCTT 2627 SEQ ID NO: 2985 -1.1 -24.2 73.1 -23.1 0 -1.9

TTGAAAGTTTGTAGTCATTT 2632 SEQ ID NO: 2986 -1.1 -18.1 58 -17 0 -4.5

GACCGCGGGCGGGGATGGGG 336 SEQ ID NO: 2987 -1 -33 82.1 -29.7 -1.9 -12.4

CGGGACAAAGCTCTTCCAGA 486 SEQ ID NO: 2988 -1 -25.1 69.7 -23 -1 -6'.8

CCATTTTGCACATAAGCCCA 1269 SEQ ID NO: 2989 -1 -25.9 70.6 -24.4 -0.1 -5

GAGGATTAAGAGCTCACTCC 1388 SEQ ID NO: 2990 -1 -23.4 69.2 -20.9 -1.4 -9.3

TCGAGGATTAAGAGCTCACT 1390 SEQ ID NO: 2991 -1 -22.2 65.6 -20.1 -0.9 -9.3

TAAATTTCTTCATAGTGGAG 2212 SEQ ID NO: 2992 -1 -17.7 56.6 -16.7 0 -4.9

TATAAGCCTAATTAATAAGA 2240 SEQ ID NO: 2993 -1 -15.1 49.6 -14.1 0 -4.7

CCCCGCTGTATAAGCCTAAT 2248 SEQ ID NO: 2994 -1 -27.1 71.6 -24.5 -1.5 -5.7

AGGGATACTGCCTGCATTTT 2580 SEQ ID NO: 2995 -1 -25.3 72.5 -23.4 -0.7 -6.7

TAAGGTCTAAGTTGCTTTAG 2668 SEQ ID NO: 2996 -1 -19.6 61.6 -18.6 0 -3.7

TCTTTCCAGGACACATGTAA 2992 SEQ ID NO: 2997 -1 -22.4 66.2 -21.4 0 -6.5

GCAAGACTTTCATACCTGTG 3169 SEQ ID NO: 2998 -1 -22.8 67 -21.8 0 -3.4

TCCACATCTGCACAGCTACC 3209 SEQ ID NO: 2999 -1 -27.3 76.5 -25.7 -0.3 -4.8

ACTATATCTTATTTGACTTT 3263 SEQ ID NO: 3000 -1 -17.7 57.1 -16.7 0 -2.4

ATCCAGAATTCATAAAGTTA 74 SEQ ID NO: 3001 -0.9 -17.5 55.1 -16.6 0 -6.6

AAGTCCGTGCTTTAAAGACT 278 SEQ ID NO: 3002 -0.9 -21.8 63.6 -20 -0.8 -8.1

GACATCTAAACTAAAGAGCA 1607 SEQ ID NO: 3003 -0.9 -17.6 54.8 -16.7 0 -4.1

CTATTAGCTGTTTGCAGGTC 2484 SEQ ID NO: 3004 -0.9 -23.8 72.4 -21.1 -1.8 -7.1

TTGTATTTTTAAATGAACTA 2797 SEQ ID NO: 3005 -0.9 -14.4 48.8 -13 -0.1 -4.5

ATACTGATAATAGTCATTTG 3133 SEQ ID NO: 3006 -0.9 -16.6 54 -15.2 -0.2 -4.1

TGACTTTAAAGTATTAATAC 3250 SEQ ID NO: 3007 -0.9 -14.1 48.3 -12 -0.1 -10.3

AAAGTTAAGAAAAAGCAAAG 102 SEQ ID NO: 3008 -0.8 -11.8 42.8 -11 0 -4.1

ATGGGGGATCCGTGTCGGTC 322 SEQ ID NO: 3009 -0.8 -29 80.1 -26.6 -1.5 -8.1

ATAGGAGTAATTCACCATTT 458 SEQ ID NO: 3010 -0.8 -20 61.1 -18.5 -0.4 -3.8

AACTATCCATATATGAATAG 1101 SEQ ID NO: 3011 -0.8 -16.2 52.1 -14.9 0 -7.5

TGCTTGCTTCGGTTAGCCTG 1231 SEQ ID NO: 3012 -0.8 -27.7 78 -26.1 -0.6 -5.1

TGAAGAAGATACTACTCCTG 1323 SEQ ID NO: 3013 -0.8 -19.3 58.8 -18.5 0 -2.2 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GTCATCAACCTTAAGTTCTC 1343 SEQ ID NO: 3014 -0.8 -21.9 66.7 -20.6 -0.1 -5.6

ACACCTTCTACCAGCTGGAA 1642 SEQ ID NO: 3015 -0.8 -25.8 72.2 -22.7 0 -12.7

CTCCCCACTCCCCCAATCTC 1907 SEQ ID NO: 3016 -0.8 -33.2 84.8 -32.4 0 -1.1

GTTCAGAGTACTTTTTTTCT 1944 SEQ ID NO: 3017 -0.8^' -20.9 66.6 -20.1 0 -6.4

TTCACAGTTTGCAATACAAA 2064 SEQ ID NO: 3018 -0.8 -18.5 56.9 -16.1 -1.5 -8.1

ATATACAAGAACCGTTCTGT 2182 SEQ ID NO: 3019 -0.8 -20.3 60.4 -18.5 -0.9 -8.9

GTGGAGCTACCACTGGGTGT

2426 SEQ ID NO: 3020 -0.8 -28.2 80.7 -24.4 -3 -11.6 ATACTGCCTGCATTTTCTTA

2576 SEQ ID NO: 3021 -0.8 -23.4 69 -22.6 0 -5.4

ATAAGATGAGGGATACTGCC 2588 SEQ ID NO: 3022 -0.8 -21.8 64.2 -20.1 -0.7 ^• -6.2

GCATAGATTAACATGCGTCA 2878 SEQ ID NO: 3023 -0.8 -21.7 63.6 -19 -1.9 -7.2

AGGACACATGTAAAAATCAC 2985 SEQ ID NO: 3024 -0.8 -17 53.3 -16.2 0 -6.3

ACTGATAATAGTCATTTGAA 3131 SEQ ID NO: 3025 -0.8 -16.8 54 -15.5 -0.2 -4.1

TAATACTGATAATAGTCATT

3135 SEQ ID NO: 3026 -0.8 -15.5 51.3 -14.2 -0.2 -4.1 GCTATTTTGTTATATCACAG

3318 SEQ ID NO: 3027 -0.8 -19.4 61 -18.6 0 -3.3

GAAAAATAACATTAAGGAAA 3349 SEQ ID NO: 3028 -0.8 -11.2 41.6 -10.4 0 -2.9

CTGCTGTAAACCATGTATCC

7 SEQ ID NO: 3029 -0.7 -23.3 66.9 -22.6 0 -4.3 CCTGCTGTAAACCATGTATC

8 SEQ ID NO: 3030 -0.7 -23.3 66.9 -22.6 0 -4.3 GACATTTTTGAAAACGACAG

663 SEQ ID NO: 3031 -0.7 -16.9 52.6 -15.6 -0.3 -5.2

TGACATCTAAACTAAAGAGC 1608 SEQ ID NO: 3032 -0.7 -16.9 53.5 -16.2 0 -2.9

GGTGGAGCTACCACTGGGTG

2427 SEQ ID NO: 3033 -0.7 -28.2 79.7 -23.7 -3.8 -12.5 TGGTGGAGCTACCACTGGGT

2428 SEQ ID NO: 3034 -0.7 -28.2 79.7 -23.7 -3.8 -12.5 CTTACATAAGATGAGGGATA

2593 SEQ ID NO: 3035 -0.7 -18.5 57.4 -17.2 -0.3 -3.5

TGAAAGTTTGTAGTCATTTC 2631 SEQ ID NO: 3036 -0.7 -18.4 59.1 -17 -0.5 -4.5

TATCACTCTCTTCCTTTCCC 3041 SEQ ID NO: 3037 -0.7 -26.5 77 -25.8 10 -0.9

GGTCTATGACTTAAAAAGGT 3064 SEQ ID NO: 3038 -0.7 -18.5 57.3 -16.8 -0.9 -5

ATAATACTGATAATAGTCAT

3136 SEQ ID NO: 3039 -0.7 -15.4 51 -14.2 -0.2 -2.8 AGGAAAAAAAATCCAGAATT

84 SEQ ID NO: 3040 -0.6 -14 46.5 -11.8 -1.5 -5.2

TTTTCCGGCATCTGGCCCTG 418 SEQ ID NO: 3041 -0.6 -30.4 80.9 -27.5 -2.3 -6.6

ACCTTGCAGGCTGCCGTGAG 995 SEQ ID NO: 3042 -0.6 -30 80.9 -28.2 -0.8 -10.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CTGCTCTTGCTGCAAATAGG 1214 SEQ ID NO: 3043 -0.6 -23.7 68.6 -21.8 -1.2 -9.3

TGCCATTTTGt^ACATAAGCC 1271 SEQ ID NO: 3044 -0.6 -25 69.9 -23.7 -0.5 -5

GGTAAATGTGGTCGAGGATT 1401 SEQ ID NO: 3045 -0.6 -22 64.8 -21.4 0 -4.9

CAAACTTGGATGATGAAAAA 2777 SEQ ID NO: 3046 -0.6 -14.7 48 -14.1 0 -2:7

TTTAATATCTTTCCAGGACA

2999 SEQ ID NO: 3047 -0.6 -20.2 61.5 -19.6 0 -5.1 CTTTAATATCTTTCCAGGAC

3000 SEQ ID NO: 3048 -0.6 -20.4 62.2 -19.8 0 -5.1 ^• AAGAATTTGCGATTCTTTGT

3113 SEQ ID NO: 3049 -0.6 -19.4 59 -16 -2.8 -7.6

TTAAAGTATTAATACTTTAT 3245 SEQ ID NO: 3050 -0.6 -13.1 46.3 -8.5 -3 -16.1

GTGAAAGTTAAGAAAAAGCA 105 SEQ ID NO: 3051 -0.5 -15 49.1 -14.5 0 -4.1

GGACAAAGCTCTTCCAGATC 484 SEQ ID NO: 3052 -0.5 -23.5 68.6 -22.5 -0.2 -6.2

GAGGAGCCCATAATGGTACC 527 SEQ ID NO: 3053 -0.5 -26.2 72.6 -24.8 -0.7 -7.7

CACAGGTGAGGAGCCCATAA 534 SEQ ID NO: 3054 -0.5 -25.9 72.1 -24.6 -0.6 -5.5

TAACTATCCATATATGAATA 1102 SEQ ID NO: 3055 -0.5 -15.9 51.4 -14.9 0 -7.5

AAACTAAAGAGCACCAAGAA 1600 SEQ ID NO: 3056 -0.5 -17.2 52.7 -16.7 0 -4.1

TTCAGAGTACTTTTTTTCTT 1943 SEQ ID NO: 3057 -0.5 -19.8 63.4 -19.3 0 -5.8

GCGTTACTTGGAGCAGTTCA 1959 SEQ ID NO: 3058 -0.5 -25.5 74.3 -24.5 -0.2 -4.4

ATGAGGGATACTGCCTGCAT 2583 SEQ ID NO: 3059 -0.5 -25.6 72.5 -24.2 -0.7 -6.7

TAATGTTGTATTTTTAAATG 2802 SEQ ID NO: 3060 -0.5 -13.9 47.8 -13.4 0 -4.5

TACAGCAGACTTTGGTCTAT 3077 SEQ ID NO: 3061 -0.5 -22.4 67.9 -19.6 -2.3 -8.2

ACCTGCTGTAAACCATGTAT 9 SEQ ID NO: 3062 -0.4 -23.1 66 -22.7 0 -4.3

CTTAGTGAAAGTTAAGAAAA 109 SEQ ID NO: 3063 -0.4 -13.9 47.3 -13.5 0 -3.4

GTTCTTTGGCTTAAAGCAGA 204 SEQ ID NO: 3064 -0.4 -22.2 66.6 -19.8 -2 -7.3

GATGGGGGATCCGTGTCGGT 323 SEQ ID NO: 3065 -0.4 -29.2 79.6 -27.2 -1.5 -8.9

CAGATCTTCATCATAGGAGT 470 SEQ ID NO: 3066 -0.4 -21.6 66.7 -20.2 -0.9 -5.8

GGAAATGGTCAGGTCAGAGG 854 SEQ ID NO: 3067 -0.4 -23.2 68.7 -22.3 -0.2 -3.2

AGGCAGAGTGGATGTTTTGA 882 SEQ ID NO: 3068 -0.4 -23.4 70.3 -23 0 -4

TCTGGTAACTATCCATATAT 1107 SEQ ID NO: 3069 -0.4 -20 61.2 -18.9 -0.4 -3.6

TCAGAGTACTTTTTTTCTTC 1942 SEQ ID NO: 3070 -0.4 -20.1 64.6 -19.7 0 -6.4

TAAATATACAAGAACCGTTC 2185 SEQ ID NO: 3071 -0.4 -16.5 51.8 -16.1 0 -6.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

GTGGAGATCAGTTTAAATAT 2198 SEQ ID NO: 3072 -0.4 -18.1 57.3 -17.7 0 -4.8

CAGATTCGGTGACCACAGGG 2384 SEQ ID NO: 3073 -0.4 -25.8 72 -24.9 -0.2 -6.1

TAGCTGTTTGCAGGTCTAAG 2480 SEQ ID NO: 3074 -0.4 -23 69.8 -20.8 -1.8 -5.8

TAACATGCGTCAATTTTGTT 2870 SEQ ID NO: 3075 -0.4 -19.7 59.4 -18.8 -0.1 -5.8

CTCTTTGCATAGATTAACAT 2884 SEQ ID NO: 3076 -0.4 -19.2 59.3' -18.8 0 -3.7

TTTAAAGTATTAATACTTTA 3246 SEQ ID NO: 3077 -0.4 -13.2 46.5 -8.9 -2.8 -15.8

GGATGTTTTGAATTGCAGAG 873 SEQ ID NO: 3078 -0.3 -20.4 62.1 -20.1 0 -5.3

TAAACTAAAGAGCACCAAGA 1601 SEQ ID NO: 3079 -0.3 -17.6 53.8 -17.3 0 -4.1

AATGAGAAGGTTATTATAGG 1823 SEQ ID NO: 3080 -0.3 -16.7 53.9 -16.4 0 -2.1

ACACAGACACTCAAATTAGG 2460 SEQ ID NO: 3081 -0.3 -19.1 58.2 -18.8 0 -3.2

TGCTTTGAAAGTTTGTAGTC 2636 SEQ ID NO: 3082 -0.3 -20 62.7 -19.7 0 -4.5

ACTTTAATATCTTTCCAGGA 3001 SEQ ID NO: 3083 -0.3 -20.4 62.2 -20.1 0 -4.9

AGTATCACTCTCTTCCTTTC 3043 SEQ ID NO: 3084 -0.3 -23.7 73.3 -23.4 0 -2.4

TGGTACCCAGACACTTTATC 514 SEQ ID NO: 3085 -0.2 -23.9 69.5 -23.2 -0.2 -7.8

AACCTTAAGTTCTCTGAAGA 1337 SEQ ID NO: 3086 -0.2 -19.9 60.7 -19.7 0 -5.6

TGACCGTGTTGGTATCCATC 2150 SEQ ID NO: 3087 -0.2 -25.7 73.1 -23.9 -1.5 -5.1

TTCCAGGACACATGTAAAAA 2989 SEQ ID NO: 3088 -0.2 -18.9 56.7 -18.7 0 -6.5

ATCTTTCCAGGACACATGTA 2993 SEQ ID NO: 3089 -0.2 -23.1 68.5 -22.9 0 -7.2

TATCTTATTTGACTTTAAAG 3259 SEQ ID NO: 3090 -0.2 -15.2 50.9 -14.5 0 -8

TTCATCATAGGAGTAATTCA 464 SEQ ID NO: 3091 -0.1 -19.2 60.4 -18.6 -0.2 -3.3

TACCCAGACACTTTATCTCC 511 SEQ ID NO: 3092 -0.1 -24.8 71 -24.7 0 -2.5

CTACCACTGGGTGTGGCTGA 2420 SEQ ID NO: 3093 -0.1 -27.9 78.5 -24.6 -3.2 -7.8

CTACAAACTTGGATGATGAA 2780 SEQ ID NO: 3094 -0.1 -17.6 54.4 -17.5 0 -4.2

ATCCACATCTGCACAGCTAC 3210 SEQ ID NO: 3095 -0.1 -25.3 72.8 -24.6 -0.3 -4.8

TCCCCCTGCCCCTCAGGACC 3297 SEQ ID NO: 3096 -0.1 -37.1 92.1 -34.3 -2.7 -6.9

TGTTATATCACAGATCCCCC 3311 SEQ ID NO: 3097 -0.1 -25.7 72.3 -25.6 0 -4.5

TTAAAAATAATTACCAATCA 3369 SEQ ID NO: 3098 -0.1 -13.1 45.2 -13 0 -4.4

CATAGGAGTAATTCACCATT 459 SEQ ID NO: 3099 0 -20.6 62 -19.9 -0.4 -3.8

GATGTTTTGAATTGCAGAGG 872 SEQ ID NO: 3100 0 -20.4 62.1 -20.4 0 -5.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CAAATAGGCCATGATTTTAG 1202 SEQ ID NO: 3101 0 -19.3 58.2 -18.8 0 -7.7

TGGACACCTTCTACCAGCTG 1645 SEQ ID NO: 3102 0 -26.5 74.4 ^' -26 -0.2 -7.8

CGTTACTTGGAGCAGTTCAG 1958 SEQ ID NO: 3103 0 -23.7 70.1 -23.2 -0.2 -4.1

AATCCCCCGCTGTATAAGCC 2252 SEQ ID NO: 3104 0 -28.9 75.1 -27.3 -1.5 -5.'7

GTCTATGACTTAAAAAGGTC 3063 SEQ ID NO: 3105 0 -17.7 56.1 -17.2 -0.2 -4.2

AATAATACTGATAATAGTCA 3137 SEQ ID NO: 3106 0 -14.7 49.3 -14.2 -0.1 -2.7

GTTATATCACAGATCCCCCT 3310 SEQ ID NO: 3107 0 -26.6 74.3 -26.6 0 -4.5

AATAACATTAAGGAAATTAC 3345 SEQ ID NO: 3108 0 -12.7 44.7 -12.7 0 -3.2

ACCAATCAGAAAAATAACAT 3357 SEQ ID NO: 3109 0 -15 48.5 -15 0 -2.9

ACGAAGTTTTGCCACTAACT 1541 SEQ ID NO: 3110 0.1 -22.1 63.6 -21.6 . -0.3 -4

AGTTCAGAGTACTTTTTTTC 1945 SEQ ID NO: 3111 0.1 -20 64.6 -20.1 0 -6.4

ATCTGTGAGTTCAATCCACT 2133 SEQ ID NO: 3112 0.1 -23 68.8 -22.2 -0.8 -4.1

GGTGTGGCTGACACAGGTCC 2411 SEQ ID NO: 3113 0.1 -28.7 82.2 -25.7 -3.1 -8.9

TCTTTGCATAGATTAACATG 2883 SEQ ID NO: 3114 0.1 -18.3 57.3 -18.4 0 -3.4

TCTCTTTGCATAGATTAACA 2885 SEQ ID NO: 3115 0.1 -19.6 60.8 -19.7 0 -3.7

AAAGGTCAGTATCACTCTCT 3050 SEQ ID NO: 3116 0.1 -21.8 67.1 -21.9 0 -2.5

CCAATCAGAAAAATAACATT 3356 SEQ ID NO: 3117 0.1 -14.9 48.3 -15 0 -2.9

AAGGAAAAAAAATCCAGAAT 85 SEQ ID NO: 3118 0.2 -13.2 44.9 -11.8 -1.5 -4.7

AGTTCTTTGGCTTAAAGCAG 205 SEQ ID NO: 3119 0.2 -21.6 65.5 -19.8 -2 -7.3

TAGGAGTAATTCACCATTTT 457 SEQ ID NO: 3120 0.2 -20.1 61.5 -19.6 -0.4 -3.8

GTGAGGAGCCCATAATGGTA 529 SEQ ID NO: 3121 0.2 -25.2 71.6 -24.5 -0.7 -5.5

AACACTTAGACATTTTTGAA 671 SEQ ID NO: 3122 0.2 -16.9 53.8 -16.5 -0.3 -2.3

GTTCAGGTGCTTGTAGTAGA 1793 SEQ ID NO: 3123 0.2 -24 74.5 -24.2 0 -3.7

TAGCGTTACTTGGAGCAGTT

1961 SEQ ID NO: 3124 0.2 -24.1 71.1 -23.4 -0.7 -4.6 TTAGCGTTACTTGGAGCAGT

1962 SEQ ID NO: 3125 0.2 -24.1 71.1 -23.4 -0.7 -4.6 CCATCTGTGAGTTCAATCCA

2135 SEQ ID NO: 3126 0.2 -24.6 71.1 -24.8 0 -3.2 TCTAAGACACAGACACTCAA

2466 SEQ ID NO: 3127 0.2 -19.7 59.9 -19.9 0 -2.5 GTCTAAGACACAGACACTCA-

2467 SEQ ID NO: 3128 0.2 -21.6 65.2 -20.4 -1.3 -5.6 CTGTTTGCAGGTCTAAGACA

2477 SEQ ID NO: 3129 0.2 -23 68.9 -21.3 -1.9 -8.8 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

TTAACATGCGTCAATTTTGT 2871 SEQ ID NO: 3130 0.2 -19.7 59.4 -19.9 0 -5

TCAGAAAAATAACATTAAGG 3352 SEQ ID NO: 3131 0.2 -13.1 45.4 -13.3 0 -3

GACCTGCTGTAAACCATGTA 10 SEQ ID NO: 3132 0.3 -23.7 67.3 -24 0 -4.3

TGGGGGATCCGTGTCGGTCC 321 SEQ ID NO: 3133 0.3 -31 83.6 -28.3 -3 -9.7

ACAGGTGAGGAGCCCATAAT 533 SEQ ID NO: 3134 0.3 -25.2 71 ' -24.7 -0.6 -5.5

GATACTGCCTGCATTTTCTT 2577 SEQ ID NO: 3135 0.3 -24.3 70.9 -24.6 0 -5.2

TAAGATGAGGGATACTGCCT 2587 SEQ ID NO: 3136 0.3 -22.7 66.1 -22.1 -0.7 -6.2

GATGTTCAATTGCAGCAAGA 2943 SEQ ID NO: 3137 0.3 -21.3 63.5 -20.9 0 -8.8

TTAATATCTTTCCAGGACAC 2998 SEQ ID NO: 3138 0.3 -20.3 61.7 -20.6 0 -5.1

ATCTTATTTGACTTTAAAGT 3258 SEQ ID NO: 3139 0.3 -16.7 54.4 -15.9 0 -10.2

CTATTTTGTTATATCACAGA 3317 SEQ ID NO: 3140 0.3 -18.2 58.1 -18.5 0 -3.3

TACCAAT(AGAAAAATAACA 3358 SEQ ID NO: 3141 0.3 -14.7 48 -15 0 -2.9

AGGAGTAATTCACCATTTTA 456 SEQ ID NO: 3142 0.4 -20.1 61.5 -19.8 -0.4 -3.8

CTGAAGAAGATACTACTCCT 1324 SEQ ID NO: 3143 0.4 -20.2 60.8 -20.6 0 -2.2

GAGAAGGTTATTATAGGGCA 1820 SEQ ID NO: 3144 0.4 -21.1 64.1 -21.5 0 -4

TTGGTGGAGCTACCACTGGG 2429 SEQ ID NO: 3145 0.4 -27.1 76.5 -23.7 -3.8 -12.5

GACACAGACACTCAAATTAG 2461 SEQ ID NO: 3146 0.4 -18.5 57 -18.9 0 -3.2

ACTTTAAAGTATTAATACTT 3248 SEQ ID NO: 3147 0.4 -14.5 49.2 -12.4 -1.4 -13

CATCATAGGAGTAATTCACC 462 SEQ ID NO: 3148 0.5 -20.9 63.1 -20.9 -0.2 -3.3

CTTCCAGATCTTCATCATAG 474 SEQ ID NO: 3149 0.5 -22 66.9 -21.5 -0.9 -5.6

ACTTAGACATTTTTGAAAAC

668 SEQ ID NO: 3150 0.5 -15.5 50.8 -15.4 -0.3 -5.2 CACTTAGACATTTTTGAAAA

669 SEQ ID NO: 3151 0.5 -16 51.6 -15.9 -0.3 -4.9 AGAGGAAATGGTCAGGTCAG

857 SEQ ID NO: 3152 0.5 -22 66.3 -22 -0.2 -2.8

ATGCAACATTTCAATGAGAA 1835 SEQ ID NO: 3153 0.5 -17.8 55 -17.7 -0.3 -7.1

TGCATAGATTAACATGCGTC 2879 SEQ ID NO: 3154 0.5 -21 62.4 -18.9 -2.6 -7.8

GACCTAAAGAATGTAAACAC 3281 SEQ ID NO: 3155 0.5 -16.5 51.8 -17 0 -4.2

ACTTTTTCCAACATTAGTGA 28 SEQ ID NO: 3156 0.6 -20.4 62 -21 0 -3.3

GGGATCCGTGTCGGTCCGGA 318 SEQ ID NO: 3157 0.6 -31.2 82 -27.7 -4.1 -11.4

AGATCTTCATCATAGGAGTA 469 SEQ ID NO: 3158 0.6 -20.6 64.7 -20.2 -0.9 -5.6 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

CTCACACTTCAAAAGTTCCA 1160 SEQ ID NO: 3159 0.6 -21.5 63.4 -21.4 -0.5 -4

ACCTTAAGTTCTCTGAAGAA 1336 SEQ ID NO: 3160 0.6 -19.9 60.7 -19.2 -1.2 0

AGCGTTACTTGGAGCAGTTC 1960 SEQ ID NO: 3161 0.6 -24.8 73.5 -24.5 -0.7 -4.6

TCAGTTTAAATATACAAGAA 2191 SEQ ID NO: 3162 0.6 -14.3 48.4 -14.9 0 -4.^P8

ACTTTGGTCTATGACTTAAA 3069 SEQ ID NO: 3163 0.6 -18.8 58.6 -18.4 -0.9 -5

AATACTGATAATAGTCATTT 3134 SEQ ID NO: 3164 0.6 -15.9 52.2 -16.5 0 -3.9

TCATAGGAGTAATTCACCAT 460 SEQ ID NO: 3165 0.7 -20.9 63.1 -21.1 -0.2 -3.3

CAGAGGAAATGGTCAGGTCA 858 SEQ ID NO: 3166 0.7 -22.7 67.3 -23.4 0.6 -2.6

GTCGAGGATTAAGAGCTCAC 1391 SEQ ID NO: 3167 0.7 -22.5 66.9 -22.1 -0.9 -9.3

CTGGACACCTTCTACCAGCT 1646 SEQ ID NO: 3168 0.7 -27.4 76.5 -26.6 -1.4 -5.4

AGCAGTTCAGAGTACTTTTT 1948 SEQ ID NO: 3169 0.7 -21.9 68.5 -22.6 0 -6.4

TTTGGTGGAGCTACCACTGG 2430 SEQ ID NO: 3170 0.7 -26 74.3 -22.9 -3.8 -12.5

ATTTGACTTTAAAGTATTAA 3253 SEQ ID NO: 3171 0.7 -14.4 48.9 -14.2 -0.2 -9.7

GGAGTAATTCACCATTTTAA 455 SEQ ID NO: 3172 0.8 -19.4 59.2 -19.7 -0.2 -3.4

GATCTTCATCATAGGAGTAA 468 SEQ ID NO: 3173 0.8 -19.9 62.2 -20.2 -0.1 -4.1

TTAAATATACAAGAACCGTT 2186 SEQ ID NO: 3174 0.8 -16.2 51 -17 0 -3.6

CAGTTTAAATATACAAGAAC 2190 SEQ ID NO: 3175 0.8 -14.1 47.8 -14.9 0 -4.8

ACAAACTTGGATGATGAAAA 2778 SEQ ID NO: 3176 0.8 -15.6 49.9 -16.4 0 -4.2

TATCTTTCCAGGACACATGT 2994 SEQ ID NO: 3177 0.8 -23.1 68.5 -23.9 0 -6.1

TATATCACAGATCCCCCTGC 3308 SEQ ID NO: 3178 0.8 -27.1 74.7 -27.2 -0.4 -4.5

ACACTTAGACATTTTTGAAA 670 SEQ ID NO: 3179 0.9 -16.9 53.8 -17.2 -0.3 -2.5

GGCAGAGTGGATGTTTTGAA 881 SEQ ID NO: 3180 0.9 -22.7 67.6 -23.6 0 -4

GTTACTTGGAGCAGTTCAGA 1957 SEQ ID NO: 3181 0.9 -23.5 71.6 -23.9 -0.2 -4.1

GGGCTATTGTAGGTACAGCT 2331 SEQ ID NO: 3182 0.9 -25.5 75.7 -25.3 -1 -6

CACAGACACTCAAATTAGGC 2459 SEQ ID NO: 3183 0.9 -20.7 61.7 -21.6 0 -3.2

TTACATAAGATGAGGGATAC 2592 SEQ ID NO: 3184 0.9 -17.8 56 -18.1 -0.3 -3.2

GACTTTAAAGTATTAATACT 3249 SEQ ID NO: 3185 0.9 -15 50.2 -14.4 -0.4 -11

GCTTAAAGCAGAAATCATTG • 196 SEQ ID NO: 3186 1 -18 55.6 -17.7 -1.2 -6.7

ATGGCCCGGCTAGGAAAGTG 1030 SEQ ID NO: 3187 1 -27 72.7 -27.3 -0.4 -8.1 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo AAGGTTATTATAGGGCACAT

1817 SEQ ID NO: 3188 1 -20.8 63 -21.8 0 -4 ACAGTTTGCAATACAAATAC

2061 SEQ ID NO: 3189 1 -17.2 54.1 -16.5 -1.7 -8.1

GGCTATTGTAGGTACAGCTG 2330 SEQ ID NO: 3190 1 -24.3 72.7 -24.2 -1 -8.6

TACATAAGATGAGGGATACT 2591 SEQ ID NO: 3191 1 -18.6 57.6 -18.5 -1 -3.9

AAAAAGGTCAGTATCACTCT 3052 SEQ ID NO: 3192 1 -19.1 59.1 -20.1 0 -2.5

CTTTGGTCTATGACTTAAAA 3068 SEQ ID NO: 3193 1 -17.9 56.1 -18.4 -0.1 -4.2

ACAGCAGACTTTGGTCTATG 3076 SEQ ID NO: 3194 1 -22.7 68.4 -21.4 -2.3 -8.2

TTTGACTTTAAAGTATTAAT 3252 SEQ ID NO: 3195 1 -14.4 48.9 -14.2 -0.4 -10.3

AGAAAAATAACATTAAGGAA 3350 SEQ ID NO: 3196 1 -11.9 43 -12.9 0 -2.9

CAGTTCTTTGGCTTAAAGCA 206 SEQ ID NO: 3197 1.1 -22.3 66.5 -21.4 -2 -7.3

GAAATGGTCAGGTCAGAGGG 853 SEQ ID NO: 3198 1.1 -23.2 68.7 -24.3 0 -2.6

CCCAGTAACCAGGAAGATGG 1448 SEQ ID NO: 3199 1.1 -24.7 68.3 -25 -0.6 -4.2

GAAGGTTATTATAGGGCACA

1818 SEQ ID NO: 3200 1.1 -21.4 64.3 -22.5 0 -4 TGCAACATTTCAATGAGAAG

1834 SEQ ID NO: 3201 1.1 -17.8 55.2 -18.3 -0.3 -5.3

TACTTGGAGCAGTTCAGAGT 1955 SEQ ID NO: 3202 1.1 -23.4 71.5 -24 -0.2 -4.1

AGTTTAAATATACAAGAACC 2189 SEQ ID NO: 3203 1.1 -15.4 50.2 -16.5 0 -4.8

CTTTGCATAGATTAACATGC 2882 SEQ ID NO: 3204 1.1 -19.7 60 -19.2 -1.5 -6.4

GGATGTTCAATTGCAGCAAG 2944 SEQ ID NO: 3205 1.1 -21.9 64.8 -22.3 0 -8.8

TCCAGGACACATGTAAAAAT 2988 SEQ ID NO: 3206 1.1 -18.8 56.4 -19.9 0 -6.5

TGCAGGCTGCCGTGAGGGGG 991 SEQ ID NO: 3207 1.2 -31.6 84.7 -31.2 -1.5 -10.1

AACGAAGTTTTGCCACTAAC 1542 SEQ ID NO: 3208 1.2 -20.5 59.9 -20.4 -1.2 -5.4

GCTTTGAAAGTTTGTAGTCA 2635 SEQ ID NO: 3209 1.2 -20.7 64.1 -21.9 0 -4.5

AAATGAACTACAAACTTGGA 2787 SEQ ID NO: 3210 1.2 -15.8 50.4 -17 0 -4.2

CTGATAATAGTCATTTGAAG 3130 SEQ ID NO: 3211 1.2 -16.6 53.7 -17.3 -0.2 -4.1

GTAACTATCCATATATGAAT 1103 SEQ ID NO: 3212 1.3 -17.4 54.7 -18.2 0 -7.5

CACAGGGCAGAGGTGCTCGG 2371 SEQ ID NO: 3213 1.3 -28.6 79.6 -27.1 -2.8 -9.4

ACCACAGGGCAGAGGTGCTC 2373 SEQ ID NO: 3214 1.3 -28.8 81.6 -27.8 -2.3 -7.5

AGACACAGACACTCAAATTA 2462 SEQ ID NO: 3215 1.3 -18.5 57 -19.8 0 -3.2

GATGAGGGATACTGCCTGCA 2584 SEQ ID NO: 3216 1.3 -26.2 73.8 -26.6 -0.7 -6.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo ACTACAAACTTGGATGATGA 2781 SEQ ID NO: 3217 1.3 -18.5 56.6 -19.8 0 -4.2

CAGAAAAATAACATTAAGGA 3351 SEQ ID NO: 3218 1.3 -13.3 45.6 -14.6 0 -2.9

TGAAAGTTAAGAAAAAGCAA 104 SEQ ID NO: 3219 1.4 -13.1 45.2 -14.5 0 -4.1

CTGCCATTTTGCACATAAGC 1272 SEQ ID NO: 3220 1.4 -23.9 68.3 -24.5 -0.6 -5

ATCAACCTTAAGTTCTCTGA 1340 SEQ ID NO: 3221 1.4 -21.1 63.9 -22 -0.1 -5.6

TGCAGGTCTAAGACACAGAC 2472 SEQ ID NO: 3222 1.4 -22.4 66.9 -23.1 -0.4 -6.7

TTCTTTGGCTTAAAGCAGAA 203 SEQ ID NO: 3223 1.5 -20.3 61.3 -19.8 -2 -7.5

GGGACAAAGCTCTTCCAGAT 485 SEQ ID NO: 3224 1.5 -24.3 69.6 -24.7 -1 -6.8

TGGCCCGGCTAGGAAAGTGG 1029 SEQ ID NO: 3225 1.5 -28.2 75.1 -29 -0.4 -8.1

TCATCAACCTTAAGTTCTCT 1342 SEQ ID NO: 3226 1.5 -21.6 65.4 -23.1 , 0.1 -5.6

AGAAGGTTATTATAGGGCAC 1819 SEQ ID NO: 3227 1.5 -20.7 63.3 -22.2 0 -4

GAACTACAAACTTGGATGAT 2783 SEQ ID NO: 3228 1.5 -17.8 54.9 -19.3 0 -4.2

AAAAGGTCAGTATCACTCTC 3051 SEQ ID NO: 3229 1.5 -20.2 62.7 -21.7 0 -2.5

AGAATGTAAACACTATATCT 3274 SEQ ID NO: 3230 1.5 -16.1 52.2 -17.6 0 -4.2

TTAGTGAAAGTTAAGAAAAA 108 SEQ ID NO: 3231 1.6 -12.3 44.1 -13.9 0 -2.7

GCCCTTACAGCTTCTAGCTT 697 SEQ ID NO: 3232 1.6 -28 79.8 -27.8 -1.8 -6

AGTGGATGTTTTGAATTGCA 876 SEQ ID NO: 3233 1.6 -21 63.6 -22.6 0 -5.1

ACAGGGCAGAGGTGCTCGGG 2370 SEQ ID NO: 3234 1.6 -29.1 81.1 -27.9 -2.8 -9.4

GTATTTTTAAATGAACTACA 2795 SEQ ID NO: 3235 1.6 -15.2 50.3 -16.8 0 -4.3

TATTTGACTTTAAAGTATTA 3254 - SEQ ID NO: 3236 1.6 -14.8 50.1 -15.2 -0.1 -10.3

ATTTTGTTATATCACAGATC 3315 SEQ ID NO: 3237 1.6 -18 58 -19.6 0 -4.1

AAAGGAAAAAAAATCCAGAA 86 SEQ ID NO: 3238 1.7 -12.5 43.6 -12.6 -1.5 -4.7

CGCGGGCGGGGATGGGGGAT 333 SEQ ID NO: 3239 1.7 -32 80.7 -33.7 0 -7.3

AGGGGGCATTGTCATGCTAA 977 SEQ ID NO: 3240 1.7 -25.4 73.1 -24.8 -2.3 -6.7

ACTTGGAGCAGTTCAGAGTA 1954 SEQ ID NO: 3241 1.7 -23.4 71.5 -25.1 0.6 -4.1

CATCTGTGAGTTCAATCCAC 2134 SEQ ID NO: 3242 1.7 -22.8 68 -24.5 0 -3.5

AAGATGAGGGATACTGCCTG 2586 SEQ ID NO: 3243 1.7 -23 66.5 -23.8 -0.7 -6.2

TTATATCACAGATCCCCCTG- 3309 SEQ ID NO: 3244 1.7 -25.4 70.9 -26.6 -0.2 -4.5

TAATTACCAATCAGAAAAAT 3362 SEQ ID NO: 3245 1.7 -13.9 46.6 -15.6 0 -3.5 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo

ATAATTACCAATCAGAAAAA

3363 SEQ ID NO: 3246 1.7 -13.9 46.6 -15.6 0 -4.4 AATAATTACCAATCAGAAAA

3364 SEQ ID NO: 3247 1.7 -13.9 46.6 -15.6 0 -4.4 ACCGCGGGCGGGGATGGGGG

335 SEQ ID NO: 3248 1.8 -33.6 83.2 -33.1 -1.9 -12.4

CCACAGGGCAGAGGTGCTCG 2372 SEQ ID NO: 3249 1.8 -29.4 80.5 -29.2 -2 -9.4

TCTTATTTGACTTTAAAGTA 3257 SEQ ID NO: 3250 1.8 -16.4 53.8 -17 -0.1 -10.3

ATATCACOAGATCCCCCTGCC 3307 SEQ ID NO: 3251 1.8 -29.4 78.6 -30.5 -0.4 -4.5

TTTTGTTATATCACAGATCC 3314 SEQ ID NO: 3252 1.8 -20 62.1 -21.8 0 -4.5

TATTTTGTTATATCACAGAT 3316 SEQ ID NO: 3253 1.8 -17.3 56 -19.1 0 -3.4

AAATAACATTAAGGAAATTA 3346 SEQ ID NO: 3254 1.8 -11.8 42.9 -13.6 0 -3.2

ATTACCAATCAGAAAAATAA

3360 SEQ ID NO: 3255 1.8 -13.9 46.6 -15.7 0 -2.9 AAAATAATTACCAATCAGAA

3366 SEQ ID NO: 3256 1.8 -13.9 46.6 -15.7 0 -4.4 TCTTGTACATTGGCCCAAAC

744 SEQ ID NO: 3257 1.9 -23.8 67.5 -25.7 0 -6.6

CGTTCAGGTGCTTGTAGTAG 1794 SEQ ID NO: 3258 1.9 -24.2 72.8 -26.1 0 -3.7

TGTATTTTTAAATGAACTAC 2796 SEQ ID NO: 3259 1.9 -14.5 49 -15.9 -0.1 -4.5

TAATATCTTTCCAGGACACA 2997 SEQ ID NO: 3260 1.9 -20.9 62.6 -22.8 0 -5.1

AAATAATTACCAATCAGAAA

3365 SEQ ID NO: 3261 1.9 -13.9 46.6 -15.8 0 -4.4 GCGATCGAGCCAGTCCCAGG

390 SEQ ID NO: 3262 2 -31 81.4 -32.3 0 -8.8

CCAGATCTTCATCATAGGAG 471 SEQ ID NO: 3263 2 -22.4 67.2 -23.4 -0.9 -5.8

AGCCTGGACTTGAGGCTCAT 1184 SEQ ID NO: 3264 2 -27.3 77.7 -26.2 -3.1 -8.7

AGAAAAAGCAAAGGAAAAAA 95 SEQ ID NO: 3265 2.1 -11.2 41.4 -13.3 0 -4.1

CATAATGGTACCCAGACACT 519 SEQ ID NO: 3266 2.1 -23.3 66.2 -24.9 -0.1 -7.8

TCAACCTTAAGTTCTCTGAA 1339 SEQ ID NO: 3267 2.1 -20.4 61.8 -22 -0.1 -5.1

GAGCAGTTCAGAGTACTTTT 1949 SEQ ID NO: 3268 2.1 -22.4 69.6 -24.5 0 -6.4

GTGACCACAGGGCAGAGGTG 2376 SEQ ID NO: 3269 2.1 -27.5 78 -28.7 -0.8 -5.5

GGGTGTGGCTGACACAGGTC 2412 SEQ ID NO: 3270 2.1 -27.9 81.3 -26.9 -3.1 -8.9

ACAGACACTCAAATTAGGCT 2458 SEQ ID NO: 3271 2.1 -20.9 62.4 -23 0 -3.7

TAAATGAACTACAAACTTGG 2788 SEQ ID NO: 3272 2.1 -14.9 48.8 -17 0 -4.2

AATTACCAATCAGAAAAATA

3361 SEQ ID NO: 3273 2.1 -13.9 46.6 -16 0 -2.9 AAAAATAATTACCAATCAGA

3367 SEQ ID NO: 3274 2.1 -13.9 46.6 -16 0 -3.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TAAAAATAATTACCAATCAG 3368 SEQ ID NO: 3275 2.1 -13 45 -15.1 0 -4.4

AGTGAAAGTTAAGAAAAAGC

106 SEQ ID NO: 3276 2.2 -14.3 48 -16.5 0 -2.8 CTGGTAACTATCCATATATG

1106 SEQ ID NO: 3277 2.2 -19.6 59.7 -21.1 -0.4 -6.9

TTACTTGGAGCAGTTCAGAG 1956 SEQ ID NO: 3278 2.2 -22.3 68.2 -24 -0.2 -4:1

TTTAAATATACAAGAACCGT 2187 SEQ ID NO: 3279 2.2 -16.2 51 -18.4 0 -4

TGTTTGCAGGTCTAAGACAC 2476 SEQ ID NO: 3280 2.2 -22.3 67.4 -22.8 -1.7 -8.8

TACAAACTTGGATGATGAAA 2779 SEQ ID NO: 3281 2.2 -16 51 -18.2 0 -4.2

ATCATAGGAGTAATTCACCA 461 SEQ ID NO: 3282 2.3 -20.9 63.1 -22.5 -0.4 -3.8

CACAGTTTGCAATACAAATA 2062 SEQ ID NO: 3283 2.3 -17.7 54.8 -18.7 -1.2 -8.1

TTTGTTATATCACAGATCCC 3313 SEQ ID NO: 3284 2.3 -21.9 65.6 -24.2 0 -4.5

TAATGGTACCCAGACACTTT

517 SEQ ID NO: 3285 2.4 -22.8 65.8 -24.4 -0.6 -7.8 AACTACAAACTTGGATGATG

2782 SEQ ID NO: 3286 2.4 -17.2 53.7 -19.6 0 -3.3

TATCACAGATCCCCCTGCCC 3306 SEQ ID NO: 3287 2.4 -31.4 81.9 -33.8 0.5 -4.5

ATAATGGTACCCAGACACTT

518 SEQ ID NO: 3288 2.5 -22.7 65.4 -24.4 -0.6 -7.1 CAACCTTAAGTTCTCTGAAG

1338 SEQ ID NO: 3289 2.5 -20 60.6 -22 -0.1 -5.6

TGAGAAGGTTATTATAGGGC 1821 SEQ ID NO: 3290 2.5 -20.4 62.7 -22.9 0 -2.8

TCTGTGAGTTCAATCCACTC 2132 SEQ ID NO: 3291 2.6 -23.4 70.5 -25.1 -0.8 -4.1

AATATCTTTCCAGGACACAT 2996 SEQ ID NO: 3292 2.6 -21.2 63.2 -23.8 0 -5.1

TGCTGTAAACCATGTATCCA 6 SEQ ID NO: 3293 2.7 -23.1 66.2 -25.8 0 -4.3

ATGGTACCCAGACACTTTAT

515 SEQ ID NO: 3294 2.7 -23.5 67.9 -25.4 -0.6 -7.8 AATGGTACCCAGACACTTTA

516 SEQ ID NO: 3295 2.7 -22.8 65.8 -24.7 -0.6 -7.8 TGGGTGTGGCTGACACAGGT

2413 SEQ ID NO: 3296 2.7 -27.5 79.1 -27.1 -3.1 -8.4 CTGGGTGTGGCTGACACAGG

2414 SEQ ID NO: 3297 2.7 -27.2 77.5 -26.8 -3.1 -8.4 GCAGCAAGAATGAACCTTGA

2932 SEQ ID NO: 3298 2.7 -21.9 62.9 -23.1 -1.4 -5.9

TAAAAAGGTCAGTATCACTC 3053 SEQ ID NO: 3299 2.7 -17.9 56.6 -20.6 0 -2.5

TGGTCTATGACTTAAAAAGG 3065 SEQ ID NO: 3300 2.7 -17.3 54.4 -19 -0.9 -5

ATCAGAAAAATAACATTAAG 3353 SEQ ID NO: 3301 2.7 -11.9 43.1 -14.6 0 -2.9

GAAAGTTAAGAAAAAGCAAA 103 SEQ ID NO: 3302 2.8 -12.4 43.8 -15.2 0 -4.1

TAGTGAAAGTTAAGAAAAAG

107 SEQ ID NO: 3303 2.8 -12.2 43.9 -15 0 -2.7 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo CGATCGAGCCAGTCCCAGGG 389 SEQ ID NO: 3304 2.8 -30.4 79.7 -32.7 0 -7.7

GGCCCGGCTAGGAAAGTGGC 1028 SEQ ID NO: 3305 2.8 -30 79.3 -31.2 -1.5 -8.1

GTATAAGCCTAATTAATAAG 2241 SEQ ID NO: 3306 2.8 -15.7 51 -18.5 0 -4.7

CTGTATAAGCCTAATTAATA 2243 SEQ ID NO: 3307 2.8 -17.3 54.4 -20.1 0 -4.7

GGTCTAAGACACAGACACTC 2468 SEQ ID NO: 3308 2.8 -22.1 66.6 -22.8 -2.1 -6.2

TTGTTATATCACAGATCCCC 3312 SEQ ID NO: 3309 2.8 -23.8 69 -26.6 0 -4.5

GCGGGCGGGGATGGGGGATC 332 SEQ ID NO: 3310 2.9 -31.6 82.9 -34.5 0 -4.4

TGAACTACAAACTTGGATGA 2784 SEQ ID NO: 3311 2.9 -17.8 54.9 -20.7 0 -4.2

ACTTAAAAAGGTCAGTATCA 3056 SEQ ID NO: 3312 2.9 -17.6 55.6 -20 -0.2 -3.2

TTAATAATACTGATAATAGT 3139 SEQ ID NO: 3313 2.9 -13.4 46.7 -16.3 0 -2.5

ACAGATCCCCCTGCCCCTCA 3302 SEQ ID NO: 3314 2.9 -34.6 87.5 -36.8 -0.4 -4.5

AATCAGAAAAATAACATTAA

3354 SEQ ID NO: 3315 2.9 -11.2 41.7 -14.1 0 -2.6 GGGGGATCCGTGTCGGTCCG

320 SEQ ID NO: 3316 3 -31.8 83.2 -30.7 -4.1 -10.9

GTGGATGTTTTGAATTGCAG 875 SEQ ID NO: 3317 3 -21 63.6 -24 0 -5.3

GGTAACTATCCATATATGAA 1104 SEQ ID NO: 3318 3 -18.6 57.2 -21.1 0 -7.5

AGCTACCACTGGGTGTGGCT 2422 SEQ ID NO: 3319 3 -29.1 82.2 -29.6 -2.5 -11.7

TAAAGTATTAATACTTTATT 3244 SEQ ID NO: 3320 3 -13.1 46.3 -12.3 -2.7 -15.6

TTGACTTTAAAGTATTAATA 3251 SEQ ID NO: 3321 3 -14 48.1 -15.8 -0.4 -10.3

ATCCCCCTGCCCCTCAGGAC 3298 SEQ ID NO: 3322 3 -35.1 89 -35.9 -2.2 -7.3

CAATCAGAAAAATAACATTA

3355 SEQ ID NO: 3323 3 -12.6 44.3 -15.6 0 -2.9 GAGTGGATGTTTTGAATTGC

877 SEQ ID NO: 3324 3.1 -20.9 63.7 -24 0 -3.1

AAGACACAGACACTCAAATT 2463 SEQ ID NO: 3325 3.1 -18.1 55.7 -21.2 0 -2.9

TTTAAATGAACTACAAACTT 2790 SEQ ID NO: 3326 3.1 -13.9 47.1 -17 ' 0 -4.3

ATTAACATGCGTCAATTTTG 2872 SEQ ID NO: 3327 3.1 -18.5 56.6 -21.6 10 -4.6

TTTGGTCTATGACTTAAAAA 3067 SEQ ID NO: 3328 3.1 -16.3 52.5 -18.4 -0.9 -5

AAGAATGTAAACACTATATC 3275 SEQ ID NO: 3329 3.1 -14.5 48.7 -17.6 0 -3.7

AAGAAAAAGCAAAGGAAAAA 96 SEQ ID NO: 3330 3.2 -11.2 41.4 -14.4 0 -4.1

TCTTTGGCTTAAAGCAGAAA 202 SEQ ID NO: 3331 3.2 -19.5 59 -20.7 -2 -7.3

TCATCATAGGAGTAATTCAC 463 SEQ ID NO: 3332 3.2 -19.3 60.6 -22 -0.2 -3.3 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo ACTGGGTGTGGCTGACACAG

2415 SEQ ID NO: 3333 3.2 -26.2 75.5 -26.8 -2.6 -7.9 TTAAATGAACTACAAACTTG

2789 SEQ ID NO: 3334 3.2 -13.8 46.8 -17 0 -3.7

AGACTTTGGTCTATGACTTA 3071 SEQ ID NO: 3335 3.2 -20.8 64.4 -21.8 -2.2 -6.3

GGATGGGGGATCCGTGTCGG 324 SEQ ID NO: 3336 3.3 -29.2 78.7 -30.5 -2 -8:9

TGTATAAGCCTAATTAATAA 2242 SEQ ID NO: 3337 3.3 -15.7 50.8 -19 0 -4.7

TTTGCATAGATTAACATGCG 2881 SEQ ID NO: 3338 3.3 -19.6 58.7 -20.3 -2.6 -7.8

CAGATCCCCCTGCCCCTCAG 3301 SEQ ID NO: 3339 3.3 -34.4 87.2 -37 -0.5 -5.5

AAATAGGCCATGATTTTAGC 1201 SEQ ID NO: 3340 3.4 -20.4 60.9 -23.8 0 -6.9

TCTGAAGAAGATACTACTCC 1325 SEQ ID NO: 3341 3.4 -19.7 60.3 -23.1 0 -2.7

TACCACTGGGTGTGGCTGAC 2419 SEQ ID NO: 3342 3.4 -27.2 77.1 -27.4 -3.2 -7.8

GAAAAAGCAAAGGAAAAAAA 94 SEQ ID NO: 3343 3.5 -10.5 40.2 -14 0 -4.1

CGGCATCTGGCCCTGTTCCC 413 SEQ ID NO: 3344 3.5 -33.4 86.8 -34.6 -2.3 -6.6

CCGCGGGCGGGGATGGGGGA 334 SEQ ID NO: 3345 3.6 -34 83.8 -35.9 -1 -11.3

CCATTATGGACTCGGGTGAG 1080 SEQ ID NO: 3346 3.6 -24.8 70.1 -26.9 -1.4 -6.8

TAAGAAAAAGCAAAGGAAAA 97 SEQ ID NO: 3347 3.7 -11.6 42.2 -15.3 0 -4.1

CCATAATGGTACCCAGACAC 520 SEQ ID NO: 3348 3.7 -24.4 67.9 -27.3 -0.6 -7.8

AGGTCTAAGACACAGACACT 2469 SEQ ID NO: 3349 3.7 -21.7 65.3 -23.3 -2.1 -6.2

CCTGGACTCTGTACTTTTTC 40 SEQ ID NO: 3350 3.8 -23.9 71.4 -27.7 0 -4.8

GGCTTAAAGCAGAAATCATT 197 SEQ ID NO: 3351 3.8 -19.2 58.1 -21 -2 -7.3

CGGGGATGGGGGATCCGTGT 327 SEQ ID NO: 3352 3.8 -30 79.5 -31 -2.8 -8.9

CAGACACTCAAATTAGGCTG 2457 SEQ ID NO: 3353 3.8 -20.7 61.7 -24.5 0 -3.7

CAGGGCAGAGGTGCTCGGGC 2369 SEQ ID NO: 3354 3.9 -30.7 85 -31.8 -2.8 -9.4

CACTGGGTGTGGCTGACACA

2416 SEQ ID NO: 3355 3.9 -26.9 76.2 -27.7 -3.1 -8.4 TAATAATACTGATAATAGTC

3138 SEQ ID NO: 3356 3.9 -13.7 47.4 -17.6 0 -2.7

GGACTCTGTACTTTTTCCAA

37 SEQ ID NO: 3357 4 -23 68.3 -27 0 -5.1 TGGACTCTGTACTTTTTCCA

38 SEQ ID NO: 3358 4 -23.7 70.5 -26.9 -0.6 -5.9 GTTTAAATATACAAGAACCG

2188 SEQ ID NO: 3359 4 -16.2 51 -20.2 0 -4.8

GTTTGCAGGTCTAAGACACA- 2475 SEQ ID NO: 3360 4 -23 68.8 -25.7 -1.2 -8.8

CTTAAAAAGGTCAGTATCAC 3055 SEQ ID NO: 3361 4 -17.6 55.6 -21.6 0 -2.4 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GACTTAAAAAGGTCAGTATC 3057 SEQ ID NO: 3362 4 -17.5 55.7 -20.8 -0.5 -4.4

TAAGACACAGACACTCAAAT

2464 SEQ ID NO: 3363 4.1 -17.7 54.9 -21.8 0 -2.4 CTTTGAAAGTTTGTAGTCAT

2634 SEQ ID NO: 3364 4.1 -18.9 59.7 -23 0 -3.9

TTACCAATCAGAAAAATAAC 3359 SEQ ID NO: 3365 4.1 -14.1 47.1 -18.2 0 -2.9

GGGGATGGGGGATCCGTGTC 326 SEQ ID NO: 3366 4.2 -29.6 81.7 -31 -2.8 -8.9

TTTGAAAGTTTGTAGTCATT 2633 SEQ ID NO: 3367 4.2 -18.1 58 -22.3 0 -4.5

CTGGACTCTGTACTTTTTCC 39 SEQ ID NO: 3368 4.3 -23.9 71.4 -28.2 0 -4.8

ACCACTGGGTGTGGCTGACA 2418 SEQ ID NO: 3369 4.3 -28.2 78.8 -29.3 -3.2 -8.2

TTAAAAAGGTCAGTATCACT 3054 SEQ ID NO: 3370 4.4 -17.6 55.6 -22 0 -2.4

TTAAGAAAAAGCAAAGGAAA 98 SEQ ID NO: 3371 4.5 -12.4 43.7 -16.9 0 -4.1

TATTTTTAAATGAACTACAA 2794 SEQ ID NO: 3372 4.5 -13.3 46.1 -17.8 0 -4.6

CTAAGACACAGACACTCAAA

2465 SEQ ID NO: 3373 4.6 -18.6 56.7 -23.2 0 -2.4 TTTGCAGGTCTAAGACACAG

2474 SEQ ID NO: 3374 4.6 -21.8 65.7 -25.1 -1.2 -8.8

ATGAACTACAAACTTGGATG 2785 SEQ ID NO: 3375 4.6 -17.2 53.7 -21.8 0 -4.2

GACTTTGGTCTATGACTTAA 3070 SEQ ID NO: 3376 4.6 -20.1 62 -23.2 -1.4 -5.6

AGAATTTGCGATTCTTTGTC 3112 SEQ ID NO: 3377 4.6 -20.5 62.5 -23.2 -1.9 -5.7

TTGGTCTATGACTTAAAAAG 3066 SEQ ID NO: 3378 4.7 -16.2 52.3 -19.9 -0.9 -5

GCAGACTTTGGTCTATGACT 3073 SEQ ID NO: 3379 4.9 -23.5 70.4 -26.1 -2.3 -6.5

TTATTTGACTTTAAAGTATT 3255 SEQ ID NO: 3380 4.9 -15.2 50.9 -18.9 -0.1 -10.3

TTGCATAGATTAACATGCGT 2880 SEQ ID NO: 3381 5 -20.7 61.3 -23.1 -2.6 -7.8

GCTACCACTGGGTGTGGCTG 2421 SEQ ID NO: 3382 5.1 -29.1 81.6 -31 -3.2 -9.1

CAGACTTTGGTCTATGACTT 3072 SEQ ID NO: 3383 5.1 -21.8 66.3 -24.6 -2.3 -6.5

CAGCAGACTTTGGTCTATGA 3075 SEQ ID NO: 3384 5.2 -23.1 69.2 -26 -2.3 -8.2

CTTGGAGCAGTTCAGAGTAC 1953 SEQ ID NO: 3385 5.3 -23.4 71.5 -28.2 -0.2 -4.2

TCACAGTTTGCAATACAAAT 2063 SEQ ID NO: 3386 5.3 -18.4 56.6 -22 -1.7 -7.3

ATATCTTTCCAGGACACATG 2995 SEQ ID NO: 3387 5.4 -21.9 65.2 -27.3 0 -5.1

CTGAATTAGAAGACATTCTT 240 SEQ ID NO: 3388 5.5 -17.5 55.4 -21.6 -1.3 -6.2

AGTTCTCTGAAGAAGATACT 1330 SEQ ID NO: 3389 5.5 -19.1 60 -23.1 -1.4 -4.9

GGGGATCCGTGTCGGTCCGG 319 SEQ ID NO: 3390 5.7 -31.8 83.2 -33.4 -4.1 -10.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter-, total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo GCGGGGATGGGGGATCCGTG 328 SEQ ID NO: 3391 5.7 -30.6 80.3 -33.5 -2.8 -8.9

TTGGAGCAGTTCAGAGTACT 1952 SEQ ID NO: 3392 5.7 -23.4 71.5 -28.6 -0.2 -6.9

CAGGTCTAAGACACAGACAC 2470 SEQ ID NO: 3393 5.7 -21.5 64.5 -25.1 -2.1 -6.2

CTTTGGCTTAAAGCAGAAAT 201 SEQ ID NO: 3394 5.8 -19.1 57.7 -23.6 -1.2 -6.'5

CAGAGTACTTTTTTTCTTCC 1941 SEQ ID NO: 3395 5.8 -21.7 67.1 -27.5 0 -6.4

AATGAACTACAAACTTGGAT 2786 SEQ ID NO: 3396 5.8 -16.5 52 -22.3 0 -4.2

AGAGTACTTTTTTTCTTCCT 1940 SEQ ID NO: 3397 5.9 -21.9 68 -27.8 0 -6.4

CTTATTTGACTTTAAAGTAT 3256 SEQ ID NO: 3398 5.9 -16 52.6 -20.7 -0.1 -10.3

TCTCTGAAGAAGATACTACT

1327 SEQ ID NO: 3399 6.1 -18.6 58.4 -24.2 -0.1 -3 TTGCAGGTCTAAGACACAGA

2473 SEQ ID NO: 3400 6.1 -22.3 66.7 -27.1 . -1.2 -8.8

CGGGCGGGGATGGGGGATCC 331 SEQ ID NO: 3401 6.3 -31.8 82 -36.4 -1.7 -7.7

AGCAGACTTTGGTCTATGAC 3074 SEQ ID NO: 3402 6.3 -22.6 68.6 -26..6 -2.3 -8.2

ATTTTTAAATGAACTACAAA 2793 SEQ ID NO: 3403 6.4 -12.9 45.2 -19.3 0 -4.6

AAAAGCAAAGGAAAAAAAAT

92 SEQ ID NO: 3404 6.5 -9.9 39.2 -16.4 0 -4.1 AGATCCCCCTGCCCCTCAGG

3300 SEQ ID NO: 3405 6.5 -34.9 88.8 -39.1 -2.3 -9.1

TGACTTAAAAAGGTCAGTAT

3058 SEQ ID NO: 3406 6.6 -17.1 54.4 -22.4 -1.2 -5.1 GTTCTCTGAAGAAGATACTA

1329 SEQ ID NO: 3407 6.7 -18.8 59.3 -24 -1.4 -4.9

CATCAACCTTAAGTTCTCTG 1341 SEQ ID NO: 3408 6.7 -21.2 63.8 -27.4 -0.1 -5.6

AAATCCCCCGCTGTATAAGC 2253 SEQ ID NO: 3409 6.9 -26.2 69.8 -31.9 -1.1 -5.3

GATCCCCCTGCCCCTCAGGA 3299 SEQ ID NO: 3410 6.9 -35.5 89.6 -39.7 -2.7 -8.5

ATCAGTTTAAATATACAAGA 2192 SEQ ID NO: 3411 7.1 -15 50 -22.1 0 -4.3

TGGAGCTACCACTGGGTGTG 2425 SEQ ID NO: 3412 7.1 -27 76.8 -32.8 -1.2 -7.7

CTATGACTTAAAAAGGTCAG 3061 SEQ ID NO: 3413 7.1 -16.8 53.4 -22.3 -1.6 -5.9

AAAAAGCAAAGGAAAAAAAA

93 SEQ ID NO: 3414 7.2 -9.2 38.1 -16.4 0 -3.3 TTCTCTGAAGAAGATACTAC

1328 SEQ ID NO: 3415 7.2 -17.8 56.7 -24 -0.9 -3.7 ATGACTTAAAAAGGTCAGTA

3059 SEQ ID NO: 3416 7.2 -17.1 54.4 -22.7 -1.6 -5.9 TTTGGCTTAAAGCAGAAATC

200 SEQ ID NO: 3417 7.3 -18.6 57.1 -23.9 -2 -7.3

GGGATGGGGGATCCGTGTCG• 325 SEQ ID NO: 3418 7.4 -29.2 78.7 -33.8 -2.8 -8.9

TATGACTTAAAAAGGTCAGT

3060 SEQ ID NO: 3419 7.4 -17.1 54.4 -22.9 -1.6 -5.9 kcal/ mol kcal/mol deg C kcal/mol kcal/mol kcal/mol

Intra- Inter- total duplex Tm of target molecular molecular position oligo binding formation Duplex structure oligo oligo TCTATGACTTAAAAAGGTCA 3062 SEQ ID NO: 3420 7.4 -17.2 54.5 -23.1 -1.4 -5.6

AGCAAAGGAAAAAAAATCCA

89 SEQ ID NO: 3421 7.7 -15.1 48.2 -21.2 -1.5 -6.2 AAGCAAAGGAAAAAAAATCC

90 SEQ ID NO: 3422 7.7 -13.7 45.7 -20.7 -0.4 -4.9 AAAGCAAAGGAAAAAAAATC

91 SEQ ID NO: 3423 7.8 -11 41.2 -18.8 0 -4.1 TGGTAACTATCCATATATGA

1105 SEQ ID NO: 3424 7.8 -19.3 59.1 -26.5 -0.3 -7.5

CAAAGGAAAAAAAATCCAGA

87 SEQ ID NO: 3425 7.9 -13.9 46.1 -20.2 -1.5 -4.7 AGATCAGTTTAAATATACAA

2194 SEQ ID NO: 3426 7.9 -15 50 -22.9 0 -5.4 GCAGGTCTAAGACACAGACA

2471 SEQ ID NO: 3427 8 -23.1 68.2 -29 -2.1 -6.6

GCAAAGGAAAAAAAATCCAG

88 SEQ ID NO: 3428 8.3 -15.1 48.2 -22.5 -0.7 -5.5 GAGATCAGTTTAAATATACA

2195 SEQ ID NO: 3429 8.5 -16.3 53.1 -24.8 0 -5.4 ATGAGAAGGTTATTATAGGG

1822 SEQ ID NO: 3430 8.7 -18.6 58.5 -27.3 0 -2.1

TGGAGATCAGTTTAAATATA 2197 SEQ ID NO: 3431 8.8 -16.6 53.8 -25.4 0 -5.4

GAGCTACCACTGGGTGTGGC

2423 SEQ ID NO: 3432 9.1 -28.8 81.5 -34.7 -3.2 -12.7 TTTTTAAATGAACTACAAAC

2792 SEQ ID NO: 3433 9.1 -13.1 45.6 -22.2 0 -4.6

TTTTAAATGAACTACAAACT 2791 SEQ ID NO: 3434 9.2 -13.9 47.1 -23.1 0 -4.6

GATCAGTTTAAATATACAAG 2193 SEQ ID NO: 3435 9.3 -15 50 -24.3 0 -4.8

CTCTGAAGAAGATACTACTC 1326 SEQ ID NO: 3436 9.4 -18.6 58.4 -27.5 -0.1 -3

GGAGCTACCACTGGGTGTGG

2424 SEQ ID NO: 3437 9.5 -28.2 79.7 -34.7 -3 -11.2 CCACTGGGTGTGGCTGACAC

2417 SEQ ID NO: 3438 9.7 -28.2 78.8 -35.6 -2.3 -8.2

GGAGATCAGTTTAAATATAC

2196 SEQ ID NO: 3439 9.9 -16.8 54.3 -26.7 0 -5.4 AGATGAGGGATACTGCCTGC

2585 SEQ ID NO: 3440 10.1 -25.5 73 -34.7 -0.7 -6.7

GGCGGGGATGGGGGATCCGT

329 SEQ ID NO: 3441 12.9 -31.8 82.9 -42.7 -2 -8.9 GGGCGGGGATGGGGGATCCG

330 SEQ ID NO: 3442 14.9 -31.8 82 -43.9 -2.8 -8.9

Example 17

Western blot analysis of LRHlprotein levels

[00194] Western blot analysis (immunoblot analysis) is carried out using 5 standard methods. Cells are harvested 16-20 h after oligonucleotide treatment, washed once with PBS, suspended in Laemmli buffer (100 ul/well), boiled for 5 minutes and loaded on a 16% SDS-PAGE gel. Gels are run for 1.5 hours at 150 V, and transferred to membrane for western blotting. Appropriate primary antibody directed to LRHlis used, with a radiolabelled or fluorescently labeled secondary antibody directed against the primary antibody species. Bands are visualized using a PHOSPHORIMAGER™ (Molecular Dynamics, Sunnyvale CA).

Claims

WHAT IS CLAIMED IS:

1. An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding LRHl, wherein said antisense compound specifically hybridizes with and inhibits the expression of LRH 1.

2. The antisense compound of claim 1 which is an antisense oligonucleotide.

3. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

4. The antisense compound of claim 3 wherein the modified internucleoside linkage is a phosphorothioate linkage.

5. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

6. The antisense compound of claim 5 wherein the modified sugar moiety is a 2'-O-methoxyethyl sugar moiety.

7. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

8. The antisense compound of claim 7 wherein the modified nucleobase is a 5-methylcytosine.

9. The antisense compound of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

10. A composition comprising the antisense compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

11. The composition of claim 10 further comprising a colloidal dispersion system.

12. The composition of claim 11 wherein the antisense compound is an antisense oligonucleotide.

13. A method of inhibiting the expression of LRH 1 in cells or tissues comprising contacting said cells or tissues with the antisense compound of claim 1 so that expression of LRHl is inhibited.

14. A method of treating a human having a disease or condition associated with LRHl comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of claim 1 so that expression of LRHl is inhibited.

15. The method of claim 14 wherein the disease or condition is involved with aromatase activity and/or breast cancer and/or carcinogenesis.

16. The method of claim 14 wherein the disease or condition is a dyslipidemia and the symptoms thereof, such as atherosclerosis, low HDL, elevated LDL, hypercholesterolemia, gall stones, hypertriglyceridemia, and obesity.

17. The method of claim 14 wherein the disease or condition is heapatitus B virus (HBV)-mediated acute or chronic hepatitis, or hepatocellular carcinoma.

18. The method of claim 14 wherein the disease or condition is ischemia/reperfusion injury.