FI110437B - Metod för framställande av en DNA-molekyl som kodar ett mutant virusprotein - Google Patents
Metod för framställande av en DNA-molekyl som kodar ett mutant virusprotein Download PDFInfo
- Publication number
- FI110437B FI110437B FI910371A FI910371A FI110437B FI 110437 B FI110437 B FI 110437B FI 910371 A FI910371 A FI 910371A FI 910371 A FI910371 A FI 910371A FI 110437 B FI110437 B FI 110437B
- Authority
- FI
- Finland
- Prior art keywords
- rex
- rev
- protein
- hiv
- gene
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 87
- 108020004414 DNA Proteins 0.000 title claims description 72
- 102000053602 DNA Human genes 0.000 title claims description 20
- 108010067390 Viral Proteins Proteins 0.000 title claims description 7
- 101710150336 Protein Rex Proteins 0.000 claims abstract description 255
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 164
- 230000014509 gene expression Effects 0.000 claims abstract description 101
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 79
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims abstract description 78
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 claims abstract description 63
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 claims abstract description 62
- 230000003612 virological effect Effects 0.000 claims abstract description 38
- 101710150344 Protein Rev Proteins 0.000 claims abstract description 31
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 claims abstract description 20
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 9
- 230000000754 repressing effect Effects 0.000 claims abstract 2
- 230000035772 mutation Effects 0.000 claims description 96
- 210000004027 cell Anatomy 0.000 claims description 93
- 102000004169 proteins and genes Human genes 0.000 claims description 88
- 108700020121 Human Immunodeficiency Virus-1 rev Proteins 0.000 claims description 54
- 108700026241 pX Genes Proteins 0.000 claims description 52
- 101900102211 Human T-cell leukemia virus 1 Protein Rex Proteins 0.000 claims description 27
- 238000004519 manufacturing process Methods 0.000 claims description 27
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 25
- 230000010076 replication Effects 0.000 claims description 24
- 230000002401 inhibitory effect Effects 0.000 claims description 19
- 108700004030 rev Genes Proteins 0.000 claims description 17
- 101150098213 rev gene Proteins 0.000 claims description 14
- 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 208000036142 Viral infection Diseases 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 230000009385 viral infection Effects 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000010367 cloning Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000001415 gene therapy Methods 0.000 claims description 4
- 230000000069 prophylactic effect Effects 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 210000004698 lymphocyte Anatomy 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000003321 amplification Effects 0.000 claims 2
- 238000003199 nucleic acid amplification method Methods 0.000 claims 2
- 101150072531 10 gene Proteins 0.000 claims 1
- 238000012217 deletion Methods 0.000 abstract description 38
- 230000037430 deletion Effects 0.000 abstract description 38
- 239000003112 inhibitor Substances 0.000 abstract description 35
- 241000894007 species Species 0.000 abstract description 24
- 230000001413 cellular effect Effects 0.000 abstract description 9
- 230000003834 intracellular effect Effects 0.000 abstract description 6
- 108700005077 Viral Genes Proteins 0.000 abstract description 3
- 239000003443 antiviral agent Substances 0.000 abstract description 3
- 238000002649 immunization Methods 0.000 abstract description 3
- 230000003053 immunization Effects 0.000 abstract description 3
- 230000002939 deleterious effect Effects 0.000 abstract description 2
- 238000010195 expression analysis Methods 0.000 abstract description 2
- 230000001052 transient effect Effects 0.000 abstract description 2
- 238000013459 approach Methods 0.000 abstract 1
- 230000006870 function Effects 0.000 description 132
- 235000018102 proteins Nutrition 0.000 description 85
- 108020004999 messenger RNA Proteins 0.000 description 80
- 235000001014 amino acid Nutrition 0.000 description 54
- 230000000694 effects Effects 0.000 description 46
- 101710149951 Protein Tat Proteins 0.000 description 45
- 229940024606 amino acid Drugs 0.000 description 42
- 239000013598 vector Substances 0.000 description 42
- 150000001413 amino acids Chemical class 0.000 description 38
- 241000700605 Viruses Species 0.000 description 37
- 210000004940 nucleus Anatomy 0.000 description 35
- 230000005764 inhibitory process Effects 0.000 description 29
- 101150103375 rex gene Proteins 0.000 description 27
- 238000001890 transfection Methods 0.000 description 25
- 230000004913 activation Effects 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 24
- 238000003556 assay Methods 0.000 description 21
- 230000027455 binding Effects 0.000 description 20
- 239000013604 expression vector Substances 0.000 description 20
- 238000001114 immunoprecipitation Methods 0.000 description 20
- 239000013612 plasmid Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 101710205625 Capsid protein p24 Proteins 0.000 description 19
- 101710177166 Phosphoprotein Proteins 0.000 description 19
- 101710149279 Small delta antigen Proteins 0.000 description 19
- 102100022563 Tubulin polymerization-promoting protein Human genes 0.000 description 19
- 238000003776 cleavage reaction Methods 0.000 description 19
- 230000007017 scission Effects 0.000 description 19
- 108091034117 Oligonucleotide Proteins 0.000 description 17
- 108091026890 Coding region Proteins 0.000 description 16
- 125000000539 amino acid group Chemical group 0.000 description 16
- 239000012634 fragment Substances 0.000 description 16
- 230000026731 phosphorylation Effects 0.000 description 16
- 238000006366 phosphorylation reaction Methods 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 15
- 108010078428 env Gene Products Proteins 0.000 description 15
- 230000002068 genetic effect Effects 0.000 description 15
- 230000004853 protein function Effects 0.000 description 14
- 108010038751 tax Gene Products Proteins 0.000 description 14
- 230000001086 cytosolic effect Effects 0.000 description 13
- 230000004807 localization Effects 0.000 description 13
- 230000004071 biological effect Effects 0.000 description 12
- 102000034356 gene-regulatory proteins Human genes 0.000 description 12
- 108091006104 gene-regulatory proteins Proteins 0.000 description 12
- 208000015181 infectious disease Diseases 0.000 description 12
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 11
- 108091023040 Transcription factor Proteins 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 108700004025 env Genes Proteins 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 230000001177 retroviral effect Effects 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 10
- 230000002950 deficient Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 239000006228 supernatant Substances 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 102100034353 Integrase Human genes 0.000 description 9
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 9
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 108091027981 Response element Proteins 0.000 description 9
- 102000040945 Transcription factor Human genes 0.000 description 9
- 210000000805 cytoplasm Anatomy 0.000 description 9
- 239000012636 effector Substances 0.000 description 9
- 101150030339 env gene Proteins 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 230000014616 translation Effects 0.000 description 9
- 101800004419 Cleaved form Proteins 0.000 description 8
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 8
- 235000003704 aspartic acid Nutrition 0.000 description 8
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 108091008146 restriction endonucleases Proteins 0.000 description 8
- 235000004400 serine Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 101710177291 Gag polyprotein Proteins 0.000 description 7
- 108700020123 Human Immunodeficiency Virus-2 rev Proteins 0.000 description 7
- 101710125418 Major capsid protein Proteins 0.000 description 7
- 108010021466 Mutant Proteins Proteins 0.000 description 7
- 102000008300 Mutant Proteins Human genes 0.000 description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
- 238000010166 immunofluorescence Methods 0.000 description 7
- 238000002703 mutagenesis Methods 0.000 description 7
- 231100000350 mutagenesis Toxicity 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 6
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 6
- 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 6
- 101710172711 Structural protein Proteins 0.000 description 6
- 201000006966 adult T-cell leukemia Diseases 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000001962 electrophoresis Methods 0.000 description 6
- 239000013613 expression plasmid Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 230000030648 nucleus localization Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 125000003607 serino group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 6
- 230000004960 subcellular localization Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 241001430294 unidentified retrovirus Species 0.000 description 6
- 230000029812 viral genome replication Effects 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 239000011543 agarose gel Substances 0.000 description 5
- 230000002788 anti-peptide Effects 0.000 description 5
- 230000002860 competitive effect Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000002458 infectious effect Effects 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 5
- 230000006911 nucleation Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 4
- 241001524679 Escherichia virus M13 Species 0.000 description 4
- 108700024394 Exon Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 230000004570 RNA-binding Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 238000010899 nucleation Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- ZBFPLELNWIASCT-UHFFFAOYSA-N 4-phenyl-4,5-dihydro-1,3-oxazol-2-amine Chemical group C1OC(N)=NC1C1=CC=CC=C1 ZBFPLELNWIASCT-UHFFFAOYSA-N 0.000 description 3
- 102000012410 DNA Ligases Human genes 0.000 description 3
- 108010061982 DNA Ligases Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000012761 co-transfection Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000013600 plasmid vector Substances 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 3
- 241001515965 unidentified phage Species 0.000 description 3
- YBNPKPVDURZUQN-KNIFDHDWSA-N (2s)-2-aminobutanedioic acid;(2s)-2-amino-4-methylpentanoic acid Chemical compound CC(C)C[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC(O)=O YBNPKPVDURZUQN-KNIFDHDWSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241001559589 Cullen Species 0.000 description 2
- 241000450599 DNA viruses Species 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 241001131785 Escherichia coli HB101 Species 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 208000037952 HSV-1 infection Diseases 0.000 description 2
- 101900141355 Human T-cell leukemia virus 1 Protein Tax-1 Proteins 0.000 description 2
- 101000756400 Human T-cell leukemia virus 2 Protein Rex Proteins 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108010087302 Viral Structural Proteins Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 239000013000 chemical inhibitor Substances 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- BXKDSDJJOVIHMX-UHFFFAOYSA-N edrophonium chloride Chemical compound [Cl-].CC[N+](C)(C)C1=CC=CC(O)=C1 BXKDSDJJOVIHMX-UHFFFAOYSA-N 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000012133 immunoprecipitate Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000012205 qualitative assay Methods 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- FLNVBBPBGKOJHN-KKAOYSRWSA-N sivmac Chemical compound O=C([C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(O)=O FLNVBBPBGKOJHN-KKAOYSRWSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 101150027303 tax gene Proteins 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000006648 viral gene expression Effects 0.000 description 2
- 230000006490 viral transcription Effects 0.000 description 2
- -1 β-cyanoethyl Chemical group 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 101150029062 15 gene Proteins 0.000 description 1
- 101150098072 20 gene Proteins 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101100098985 Caenorhabditis elegans cct-3 gene Proteins 0.000 description 1
- 241001247437 Cerbera odollam Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241001101077 Crex Species 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 102100028285 DNA repair protein REV1 Human genes 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 102100038796 E3 ubiquitin-protein ligase TRIM13 Human genes 0.000 description 1
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241001272023 Gelidium rex Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000175212 Herpesvirales Species 0.000 description 1
- 101000664589 Homo sapiens E3 ubiquitin-protein ligase TRIM13 Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101000617808 Homo sapiens Synphilin-1 Proteins 0.000 description 1
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 241000701460 JC polyomavirus Species 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100205189 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-5 gene Proteins 0.000 description 1
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 1
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 1
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 108010034634 Repressor Proteins Proteins 0.000 description 1
- 102000009661 Repressor Proteins Human genes 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 101150036912 Segment-5 gene Proteins 0.000 description 1
- 241000713311 Simian immunodeficiency virus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 101001039853 Sonchus yellow net virus Matrix protein Proteins 0.000 description 1
- 102100021997 Synphilin-1 Human genes 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 241000736878 Tamias Species 0.000 description 1
- 108010052104 Viral Regulatory and Accessory Proteins Proteins 0.000 description 1
- 241000713325 Visna/maedi virus Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000006154 adenylylation Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000013098 chemical test method Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 108091092330 cytoplasmic RNA Proteins 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000007457 establishment of nucleus localization Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000012224 gene deletion Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000014726 immortalization of host cell Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 108010066381 preproinsulin Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 208000007153 proteostasis deficiencies Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 108700004027 tat Genes Proteins 0.000 description 1
- 101150098170 tat gene Proteins 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000037426 transcriptional repression Effects 0.000 description 1
- 208000037918 transfusion-transmitted disease Diseases 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000035903 transrepression Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1036—Retroviridae, e.g. leukemia viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/14011—Deltaretrovirus, e.g. bovine leukeamia virus
- C12N2740/14022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
- C12N2740/16322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (19)
1. Metod för framställande av en DNA-molekyl som kodar ett mutant virusprotein, kännetecknat därav, att proteinet är en för virusfunktionen väsentlig gens 5 produkts modifierad form och transdominant represserar en eller flera av följande geners fenotypiska expression: i) HTLV-I's eller HTLV-II's vildtyp rex gen, varvid det mutanta virusproteinet är modifierat frän
2. Metod enligt patentkrav 1, kännetecknat därav, att HTLV-I's rex gens fenotypiska expression represseras.
3. Metod enligt patentkrav 1 kännetecknat därav, att den i patentkrav 1 definierade DNA- 25 molekylen, som kodar HTLV-I Rex protein, framställs genom mutation i vildtyp Rex proteinet enligt bild 1 mellan aminosyrapositionerna 30 och 101, fördelaktigt mellan 82-97, fördelaktigare mellan 87-94; eller genom mutation i vildtyp Rex proteinet enligt bild 1 mellan 30 aminosyrapositionerna 59 och 121, fördelaktigt i positionerna 59, 60, 64, 65 och 119, 129 eller 121.
4. Metod enligt patentkrav 3, kännetecknat därav, att den i patentkrav 3 definierade DNA- molekylen framställs frän rex-härledda pcRexM7 35 (bilderna 1, IA, 3 och 4, mutant no. 7). 110437 80
5. Metod enligt patentkrav 2, kännetecknat därav, att ytterligare represseras HIV-1 rev genens fenotypiska expression.
6. Metod enligt patentkrav 2, kännetecknat 5 därav, att den i patentkrav 4 definierade DNA- molekylen framställs frän rex-härledda pcRexM7 (bilderna 1, 1A, 3 och 4, mutant no. 7).
7. Metod enligt patentkrav 1, kännetecknat därav, att HIV-l's, HIV-2's och SIV's rev gens 10 fenotypiska expression represseras.
8. Metod enligt patentkrav 7, kännetecknat därav, att HIV-1 rev gens fenotypiska expression represseras.
9. Metod enligt patentkrav 7, kännetecknat 15 därav, att DNA-molekylen, som kodar HIV-1 Rev protein, framställs genom mutation i vildtyp Rev proteinet enligt bild 6 mellan aminosyrapositionerna 68 och 90, fordelaktigt mellan 78 och 86, fördelaktigare mellan 78 och 83 eller 84.
10. Metod enligt patentkrav 9, kännetecknat : därav, att den i patentkrav 9 definierade DNA- molekylen framställs frän rev-härledda pM32 (bilderna 5A och 6, mutant pM32) .
10 Rex proteinets vildtypsform; och ii) HIV-1's, HIV-2's eller SIV's vildtyp rev gen, varvid det mutanta virusproteinet är modifierat frän Rev proteinets vildtypsform, innefattande isolerande av motsvarande vildtyp gen frän ett lämpligt 15 expressionssystem, ställande av denna gen i ett lämpligt kloningssystem, förande av den eftersökta mutationen i genen och tillvaratagande av den erhällna mutantgenen, med den eftersökta mutationen, frän klonerna.
11. Metod enligt patentkrav 9, kännetecknat 25 därav, att den i patentkrav 9 definierade DNA- molekylen framställs frän rev-härledda pMIO (bilderna 5, 6 och 7, mutant M10).
12. Metod enligt patentkrav 1, kännetecknat därav, att DNA-molekylen framställs frän rex-härledda 30 pcRexM7 (bilderna 1, 1A, 2 och 4, mutant no. 7).
13. Metod enligt patentkrav 1, kännetecknat därav, att DNA-molekylen framställs frän rev-härledda pM32 (bilderna 5A, 6, mutant pM32).
14. Metod enligt patentkrav 1, kännetecknat 35 därav, att DNA-molekylen framställs frän rev-härledda pMIO (bilderna 5, 6, 7, mutant M10) . 110437 81
15. Metod för f ramställande av ett i patentkraven 1 eller 12-14 definierat mutant virusprotein, kännetecknat därav, att metoden . i innefattar uttryckning ooh kopiering av den i 5 patentkraven 1 eller 12-14 definierade DNA-molekylen i ett lämpligt expressions- och kopieringssystem och tillvaratagande av den därav erhällna produkten.
16. Metod för framställande av en farmaceutisk sammansättning, kännetecknat därav, att metoden 10 innefattar blandning av i patentkrav 1 definierade DNA-molekylen eller proteinet i en lämplig form, för erhällande av den eftersökta profylaktiska eller terapeutiska verkan, tillsammans med en farmaceutiskt godtagbar bärare eller ett farmaceutiskt godtagbart 15 utspädningsmedel.
17. Metod för inhiberande av replikation av HIV-1 in vitro, kännetecknat därav, att metoden innefattar förande av en transdominant repressor, med en i patentkrav 1 definierad HIV-1 Rev funktion, in i 20 en HIV-1 infekterad cell.
18. Metod för f ramställande av en sammansättning, för användning inom genterapin vid behandling av virusinfektioner, kännetecknat därav, *. att metoden innefattar blandning av en i nägon av 25 patentkraven 1-14 definierad DNA-molekyl tillsammans med en farmaceutiskt godtagbar bärare eller ett farmaceutiskt godtagbart utspädningsmedel.
19. Metod enligt patentkrav 18 för framstäl-lande av en sammansättning, kännetecknat där-30 av, att sammansättningen används inom genterapin tili att skydda lymfoidcellerna hos patienter, som utsatts för virusinfektion.
Applications Claiming Priority (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US35687889A | 1989-05-25 | 1989-05-25 | |
US35687889 | 1989-05-25 | ||
GB8915602 | 1989-07-07 | ||
GB898915602A GB8915602D0 (en) | 1989-07-07 | 1989-07-07 | Multivalent repressor of gene function |
GB898924396A GB8924396D0 (en) | 1989-10-30 | 1989-10-30 | Multivalent repressor of gene function |
GB8924396 | 1989-10-30 | ||
US44267089A | 1989-11-29 | 1989-11-29 | |
US44267089 | 1989-11-29 | ||
EP9000831 | 1990-05-23 | ||
PCT/EP1990/000831 WO1990014427A2 (en) | 1989-05-25 | 1990-05-23 | Multivalent repressor of gene function |
Publications (2)
Publication Number | Publication Date |
---|---|
FI910371A0 FI910371A0 (fi) | 1991-01-24 |
FI110437B true FI110437B (sv) | 2003-01-31 |
Family
ID=27450368
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI910371A FI110437B (sv) | 1989-05-25 | 1991-01-24 | Metod för framställande av en DNA-molekyl som kodar ett mutant virusprotein |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP0406557B1 (sv) |
JP (2) | JP3126378B2 (sv) |
KR (1) | KR100215949B1 (sv) |
AT (1) | ATE207122T1 (sv) |
AU (2) | AU648256B2 (sv) |
CA (1) | CA2032158C (sv) |
DE (1) | DE69033829T2 (sv) |
DK (1) | DK0406557T3 (sv) |
ES (1) | ES2166748T3 (sv) |
FI (1) | FI110437B (sv) |
HU (2) | HU217091B (sv) |
IL (1) | IL94482A (sv) |
WO (1) | WO1990014427A2 (sv) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0554389T4 (da) * | 1990-10-17 | 2002-11-11 | Us Health | Molekylære kloner af HIV-1 og anvendelse deraf |
US5534408A (en) * | 1993-09-24 | 1996-07-09 | University Of Massachusetts Medical Center | 2-deoxystreptamine aminoglycoside inhibition of HIV RRE/Rev binding |
US5650306A (en) * | 1993-06-07 | 1997-07-22 | University Of Michigan | Recombinant nucleic acids for inhibiting HIV gene expression |
WO1995004546A1 (en) * | 1993-08-06 | 1995-02-16 | Kai Juhani Ernst Krohn | Novel mutated human and simian immunodeficiency viruses and vaccines containing said viruses |
US6228369B1 (en) | 1993-12-13 | 2001-05-08 | Transgene S.A. | Composition of trans-dominant variants of viral proteins for obtaining an anti-viral effect |
US5981258A (en) * | 1993-12-13 | 1999-11-09 | Transgene S.A. | Composition of trans-dominant variants of viral proteins for obtaining an antiviral effect |
FR2713651B1 (fr) * | 1993-12-13 | 1996-04-19 | Transgene Sa | Nouvelle composition pour un effet antiviral. |
CN1991365A (zh) | 1996-01-26 | 2007-07-04 | 沃尔科股份有限公司 | 根据人类hiv病毒株的表型药物敏感性控制hiv阳性病人化疗的方法 |
US6776986B1 (en) | 1996-06-06 | 2004-08-17 | Novartis Ag | Inhibition of HIV-1 replication by antisense RNA expression |
EP0914423A2 (en) * | 1996-06-06 | 1999-05-12 | Novartis AG | Inhibition of hiv-1 replication by antisense rna expression |
WO1997046687A1 (en) * | 1996-06-06 | 1997-12-11 | Novartis Ag | Vectors comprising sar elements |
EP1144621A2 (en) * | 1998-12-22 | 2001-10-17 | Subsidiary N0. 3, INC. | Genetic suppressor elements against human immunodeficiency virus |
WO2000040606A2 (en) * | 1999-01-06 | 2000-07-13 | The Regents Of The University Of California | Modulation of hiv replication using sam68 |
WO2004064501A2 (en) | 2003-01-23 | 2004-08-05 | Gala Design Inc. | Transgenic animals expressing transdominant negative retroviral nucleic acids and proteins |
JP5653549B1 (ja) | 2014-05-30 | 2015-01-14 | 株式会社松風 | イオン徐放性歯科用レジン系仮封材組成物 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4935372A (en) * | 1986-05-20 | 1990-06-19 | Dana Farber Cancer Institute | Art nucleotide segments, vectors, cell lines methods of preparation and use |
-
1990
- 1990-05-23 WO PCT/EP1990/000831 patent/WO1990014427A2/en active IP Right Grant
- 1990-05-23 KR KR1019910700090A patent/KR100215949B1/ko not_active IP Right Cessation
- 1990-05-23 ES ES90109892T patent/ES2166748T3/es not_active Expired - Lifetime
- 1990-05-23 IL IL9448290A patent/IL94482A/xx not_active IP Right Cessation
- 1990-05-23 EP EP90109892A patent/EP0406557B1/en not_active Expired - Lifetime
- 1990-05-23 AU AU57388/90A patent/AU648256B2/en not_active Expired
- 1990-05-23 CA CA002032158A patent/CA2032158C/en not_active Expired - Lifetime
- 1990-05-23 DE DE69033829T patent/DE69033829T2/de not_active Expired - Lifetime
- 1990-05-23 HU HU904245A patent/HU217091B/hu unknown
- 1990-05-23 AT AT90109892T patent/ATE207122T1/de not_active IP Right Cessation
- 1990-05-23 JP JP02507933A patent/JP3126378B2/ja not_active Expired - Lifetime
- 1990-05-23 DK DK90109892T patent/DK0406557T3/da active
-
1991
- 1991-01-24 FI FI910371A patent/FI110437B/sv active
-
1994
- 1994-07-20 AU AU67573/94A patent/AU678478B2/en not_active Expired
-
1995
- 1995-06-19 HU HU95P/P00249P patent/HU211530A9/hu unknown
-
1997
- 1997-11-19 JP JP31805597A patent/JP3159671B2/ja not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
JPH10165188A (ja) | 1998-06-23 |
EP0406557B1 (en) | 2001-10-17 |
AU6757394A (en) | 1994-11-17 |
IL94482A (en) | 2003-09-17 |
KR920701440A (ko) | 1992-08-11 |
JPH04500009A (ja) | 1992-01-09 |
WO1990014427A2 (en) | 1990-11-29 |
HU211530A9 (en) | 1995-11-28 |
IL94482A0 (en) | 1991-03-10 |
CA2032158A1 (en) | 1990-11-26 |
HU904245D0 (en) | 1991-06-28 |
AU648256B2 (en) | 1994-04-21 |
ATE207122T1 (de) | 2001-11-15 |
DE69033829D1 (de) | 2001-11-22 |
DK0406557T3 (da) | 2002-02-11 |
AU5738890A (en) | 1990-12-18 |
KR100215949B1 (ko) | 1999-08-16 |
JP3159671B2 (ja) | 2001-04-23 |
FI910371A0 (fi) | 1991-01-24 |
DE69033829T2 (de) | 2002-04-04 |
CA2032158C (en) | 2009-09-15 |
WO1990014427A3 (en) | 1991-01-10 |
HUT56135A (en) | 1991-07-29 |
EP0406557A3 (en) | 1991-05-02 |
HU217091B (hu) | 1999-11-29 |
JP3126378B2 (ja) | 2001-01-22 |
ES2166748T3 (es) | 2002-05-01 |
EP0406557A2 (en) | 1991-01-09 |
AU678478B2 (en) | 1997-05-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FI110437B (sv) | Metod för framställande av en DNA-molekyl som kodar ett mutant virusprotein | |
Ruben et al. | Structural and functional characterization of human immunodeficiency virus tat protein | |
McDougall et al. | Defective endogenous proviruses are expressed in feline lymphoid cells: evidence for a role in natural resistance to subgroup B feline leukemia viruses | |
Malim et al. | Functional dissection of the HIV-1 Rev trans-activator—derivation of a trans-dominant repressor of Rev function | |
US5686264A (en) | Compositions and methods relating to transdominant Tat mutants | |
Nolan et al. | The bcl-3 proto-oncogene encodes a nuclear IκB-like molecule that preferentially interacts with NF-κB p50 and p52 in a phosphorylation-dependent manner | |
Guy et al. | HIV F/3'orf encodes a phosphorylated GTP-binding protein resembling an oncogene product | |
US8197821B2 (en) | Human immunodeficiency virus integrase—Transportin—SR protein—protein interactions | |
Walker et al. | The v-rel oncogene: insights into the mechanism of transcriptional activation, repression, and transformation | |
Deen et al. | Murine mammary tumor virus pol-related sequences in human DNA: characterization and sequence comparison with the complete murine mammary tumor virus pol gene | |
Degols et al. | Antiviral activity and possible mechanisms of action of oligonucleotides-poly (L-lysine) conjugates targeted to vesicular stomatitis virus mRNA and genomic RNA | |
Berberich et al. | Mutations in the regions of the Rous sarcoma virus 3'splice sites: implications for regulation of alternative splicing | |
US5871958A (en) | Mutant rev genes encoding transdominant repressors of HIV replication | |
US6162898A (en) | Mutant Rev transdominant repressors of HIV replication | |
AU720284B2 (en) | Multivalent repressor of gene function | |
US5652340A (en) | Matrix-associating DNA-binding protein, nucleic acids encoding the same and methods for detecting the nucleic acids | |
IE83555B1 (en) | Multivalent repressor of gene function | |
Delahunty | Studies of retroviral protein-nucleic acid interactions | |
Ogert | Avian retroviral RNA export | |
Schiltz | Translational studies of equine infectious anemia virus RNA and analysis of the viral regulatory proteins | |
Bakker | The regulation of RNA processing by the Rex protein of human T cell leukemia virus type II | |
Kabrun | Biochemical and biological characterization of c and v-rel | |
Hodge | Regulation of human immunodeficiency virus expression by viral and cellular factors | |
Dunn | Transcriptional Regulation and Cell Transformation by v-Jun | |
Lee | Differential gene expression of the HIV-1 LTR by Tat in human and rodent cells |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
GB | Transfer or assigment of application |
Owner name: NOVARTIS AG |