WO2004098646B1 - Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues - Google Patents

Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues

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Publication number
WO2004098646B1
WO2004098646B1 PCT/IB2004/001973 IB2004001973W WO2004098646B1 WO 2004098646 B1 WO2004098646 B1 WO 2004098646B1 IB 2004001973 W IB2004001973 W IB 2004001973W WO 2004098646 B1 WO2004098646 B1 WO 2004098646B1
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WO
WIPO (PCT)
Prior art keywords
cell
pancreatic
polypeptide
nucleic acid
promoter
Prior art date
Application number
PCT/IB2004/001973
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French (fr)
Other versions
WO2004098646A1 (en
Inventor
Sarah Ferber
Original Assignee
Sarah Ferber
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sarah Ferber filed Critical Sarah Ferber
Priority to EP04732369A priority Critical patent/EP1624898A1/en
Priority to JP2006506631A priority patent/JP2006525994A/en
Priority to AU2004236573A priority patent/AU2004236573B2/en
Publication of WO2004098646A1 publication Critical patent/WO2004098646A1/en
Publication of WO2004098646B1 publication Critical patent/WO2004098646B1/en

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    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
    • C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian
    • 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
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Endocrinology (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Plant Pathology (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Biochemistry (AREA)
  • Emergency Medicine (AREA)
  • Biophysics (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present application concerns methods of inducing a pancreatic endocrine phenotype and function, including pancreatic hormone production, in a non-pancreatic and non-endocrine cell/tissue, particularly in a liver cell/tissue. This is achieved by contacting said non-pancreatic and non-endocrine cell/tissue with a PDX-1 inducer compound, such as a nucleic acid encoding a PDX-1 polypeptide, a neuroD polypeptide or a betacellulin peptide, eventually in the presence of nicotinamide, EGF, activin A, HGF, exedin GLP-1 or betacellulin.

Claims

AMENDED CLAIMS [received by the International Bureau on 16 December 2004 (16.12.2004); original claims 1-34 replaced by new claims 1-43 (5 pages)]+ STATEMENT
1. An in vitro method of inducing endogenous PDX-1 expression in a non- pancreatic cell, said method comprising introducing to said cell a composition comprising a nucleic acid encoding a neuroD polypeptide or a betacellulin polypeptide, in an amount sufficient to induce said endogenous PDX-1 expression in said cell.
2. The method of claim 1, wherein said nucleic acid is operably linked to a promoter.
3. The method of claim 2, wherein said promoter is a cytomegalovirus (CMV) promoter, a BOS promoter, a transthyretin promoter, a glucose 6-phosphatase promoter, an albumin intestinal fatty acid binding protein promoter, a thyroglobulin promoter, a surfactant A promoter, a surfactant c promoter or a phosphoglycerate kinase 1 promoter.
4. The method of claim 1, 2 or 3, wherein said nucleic acid is present in a plasmid.
5. The method of claim 1,2 or 3 wherein said nucleic acid is present in a viral vector.
6. The method of claim 5, wherein said viral vector is an adenovirus vector or a lentivirus vector.
7. The method of claim 6 wherein said adenovirus vector is a gutless recombinant adenovirus vector.
8. The method of claim 1, wherein said cell is an endodermal cell, an ectodermal cell or a mesodeπnal cell.
79
9. The method of claim 8, wherein said endodermal cell is a liver cell.
10. The method of claim 8, wherein said ectodermal cell is a skin cell,
11. The method of claim 8, wherein said mesoderma] cell is a bone marrow cell.
12. The method of claim 1, further comprising contacting said cell with a transfection agent.
13. The method of claim 1, further comprising contacting said cell with a composition comprising icotinamide, epidermal growth factor, activin A, hepatic growth factor, exendin, GLP-1 or betacellulin.
14. An in vitro method of inducing the expression of a pancreatic gene in a non-pancreatic cell, said method comprising introducing to said cell a composition comprising a nucleic acidencoding a neuroD polypeptide or a betacellulin polypeptide, in an amount sufficient to induce said gene expression, in said cell.
15. The method of claim 14, wherein said pancreatic gene is a pancreatic transcription factor.
16. The method of claim 15, wherein said pancreatic transcription factor is beta 2, ΪSL-2, Nkx6.1, Ngn3.1 , or NKx2.2.
17. The method of claim 14, wherein said pancreatic gene is an endocrine gene or an exocrine gene.
18. The method of claim 17, wherein said endocrine gene is SCG2, SGNE1, CHGN, PTPRN, AMPH, BEA, NeuroD or folistatin.
80
19. The method of claim 17, wherein said exocrine gene is serine protease inhibitor, Kazal type 1, Elastase, factor-ρ48, or regenerating islet-derived 1 alpha.
20. The method of claim 14, wherein said cell is an endodermal cell, an ectodermal cell or a mesodermal cell.
21. The method of claim 20, wherein said endodermal cell is a liver cell.
22. .The method of claim 20, wherein said ectodermal cell is a skin cell.
23. The method of claim 20, wherein said mesodermal cell is a bone marrow cell.
24. A method of converting a non-pancreatic cell to a pancreatic cell, comprising contacting said non-pancreatic cell with a nucleic acid encoding a neuroD polypeptide or a betacellulin polypeptideϊn an amount to a. induce the expression of endogenous PDX-l, an embryonic marker, insulin, glucogon, or somatostatin in said non-pancreatic cell or b. repress the expression of C/EBPβ, albumin or ADH-1 in said non- pancreatic cell.
25. The method of claim 24, wherein said embryonic marker is alpha-1 fetop otein or Gata-4.
26. The method of claim 24, wherein said non-pancreatic cell is a differentiated cell.
27. The method of claim 26, wherein said differentiated cell is a liver cell, a skin cell or a bone marrow cell.
28. Use of a neuroD or a betacellulin polypeptide or a nucleic acid encoding a neuroD or a betacellulin polypeptide in manufacture of a medicament for treating a pancreatic associated disorder in a subject, wherein said medicament induces
81 endogenous PDX-1 expression in a non-pancreatic cell.
29. Use according to claim 28, wherein said medicament induces or enhances a pancreatic islet cell phenotype in a non-pancreatic islet cell in said subject.
30. Use according to claim 28, wherein said medicament induces a pancreatic islet gene expression profile in a subject.
31. Use according to claim 28, wherein said nucleic acid is a DNA molecule.
32. Use according to claim 28, wherein said nucleic acid is present in a plasmid or a viral vector, or is encapsulated in a virus.
33. Use according to claim 32, wherein said virus is hepatotrophic.
34. Use according to claim 28, 29, or 30, wherein said polypeptide or a nucleic acid encoding a PDX polypeptide increases hepatic insulin levels or serum insulin levels.
35. Use according to claim 28, 29, or 30, wherein the subject is a rodent or human.
36. Use according to claim 28, 29, or 30, wherein the PDX polypeptide or a nucleic acid encoding a PDX polypeptide is for administration in association with a transfection agent.
37. Use according to claim 28, 29, or 30, wherein the PDX polypeptide or a nucleic acid encoding a PDX polypeptide is for administration by a route selected from the group consisting of intraperitoneal, subcutaneous, nasal, intravenous, oral and transdermal delivery.
38. Use according to claim 28, 29, or 30, wherein the polypeptide- or a
82 nucleic acid is for intravenous administration.
39. Use according to claim 28, wherein said pancreatic disorder is diabetes.
40. The method of claim 28, wherein said cell is an endodermal cell, an ectodermal cell or a mesodermal cell.
41. The method of claim 40, wherein said endodermal cell is a liver cell.
42. The method of claim 40, wherein said ectodermal cell is a skin cell.
43. The method of claim 40, wherein said mesodermal cell is a bone marrow cell,
83
PCT/IB2004/001973 2003-05-12 2004-05-12 Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues WO2004098646A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP04732369A EP1624898A1 (en) 2003-05-12 2004-05-12 Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues
JP2006506631A JP2006525994A (en) 2003-05-12 2004-05-12 Methods for inducing regulated pancreatic hormone production in non-islet tissue
AU2004236573A AU2004236573B2 (en) 2003-05-12 2004-05-12 Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US46971503P 2003-05-12 2003-05-12
US60/469,715 2003-05-12

Publications (2)

Publication Number Publication Date
WO2004098646A1 WO2004098646A1 (en) 2004-11-18
WO2004098646B1 true WO2004098646B1 (en) 2005-04-28

Family

ID=33435254

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2004/001973 WO2004098646A1 (en) 2003-05-12 2004-05-12 Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues

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EP (1) EP1624898A1 (en)
JP (2) JP2006525994A (en)
AU (1) AU2004236573B2 (en)
WO (1) WO2004098646A1 (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6774120B1 (en) 1999-06-01 2004-08-10 Sarah Ferber Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues
US8778899B2 (en) 1999-06-01 2014-07-15 Sarah Ferber Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues
AU2006328988B2 (en) 2005-12-21 2012-08-02 Universite Catholique De Louvain Isolated liver stem cells
EP2082036A4 (en) * 2006-09-22 2010-06-09 Baylor Res Inst In vivo transformation of pancreatic acinar cells into insulin-producing cells
CA2904198A1 (en) * 2013-03-15 2014-09-18 Universite De Geneve Use of insulin signaling antagonists, optionally in combination of transfection of non-beta cells, for inducing insulin production
MX2015017235A (en) 2013-06-13 2017-05-04 Orgenesis Ltd Cell populations, methods of transdifferention and methods of use thereof.
US20160129047A1 (en) 2013-07-05 2016-05-12 Université Catholique de Louvain Conditioned medium from human adult liver stem cells and its use in the treatment of liver disorders
MA41296A (en) * 2014-12-30 2017-11-07 Orgenesis Ltd TRANSDIFFERENTIATION PROCESSES AND METHODS FOR USING THE SAME
US9957287B2 (en) 2016-05-26 2018-05-01 Cornell University Methods and compositions to treat type-1 and type-2 diabetes
KR20190039822A (en) * 2016-08-29 2019-04-15 해컨색 유니버시티 메디컬 센터 Composition and method for reprogramming adult cells via stem cell function of platelet-rich fraction of blood containing platelet-like cells in humans
AU2017321300B2 (en) 2016-08-29 2022-11-17 Hackensack University Medical Center Compositions and methods for programming adult cells with platelet rich fraction of blood containing platelet-like cells
SG11201911256UA (en) 2017-05-08 2020-01-30 Orgenesis Ltd Transdifferentiated cell populations and methods of use thereof
CA3070750A1 (en) * 2017-07-27 2019-01-31 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Functional feline pancreatic cells from adipose tissue
CN112899351B (en) * 2021-02-03 2022-08-26 东华大学 Double-fluorescence quantitative PCR detection kit for detecting cell infiltration state of PDX model mouse

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6774120B1 (en) * 1999-06-01 2004-08-10 Sarah Ferber Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues
EP1444345A4 (en) * 2001-10-18 2004-12-08 Ixion Biotechnology Inc Conversion of liver stem and progenitor cells to pancreatic functional cells
GB0206357D0 (en) * 2002-03-18 2002-05-01 Univ Bath Cells
JP4136434B2 (en) * 2002-04-17 2008-08-20 進 清野 Induction of insulin-producing cells

Also Published As

Publication number Publication date
AU2004236573A1 (en) 2004-11-18
JP2011068660A (en) 2011-04-07
WO2004098646A1 (en) 2004-11-18
AU2004236573B2 (en) 2009-10-22
JP2006525994A (en) 2006-11-16
EP1624898A1 (en) 2006-02-15

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