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

• US 6,774,120 B1
• Filed: 05/31/2000
• Issued: 08/10/2004
• Est. Priority Date: 06/01/1999
• Status: Expired due to Term

• Current Assignee: Tel Hashomer Medical Research Infrastructure And Services Ltd.
• Original Assignee: Sarah Ferber
• Inventors: Ferber, Sarah
• Primary Examiner(s): Reynolds, Deborah J.
• Assistant Examiner(s): WOITACH, JOSEPH T
• Application Number:
  US09/584,216
• Time in Patent Office: 1,532 Days
• Field of Search: 514/44, 536/23.1, 536/23.5, 435/325, 435/235.1, 530/350, 424/93.1, 424/191.1
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

Disclosed are methods and pharmaceutical compositions for inducing pancreatic hormone production.

Claims

1. A method of inducing pancreatic hormone expression in the liver of a mammal, wherein said pancreatic hormone is selected from the group consisting of insulin, somatostatin, and glucagon, said method comprising administering to a mammal an adenoviral particle comprising an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide in an amount sufficient to induce said pancreatic hormone expression in said liver in said mammal.

2. The method of claim 1, wherein administering said vector increases hepatic insulin levels in said mammal.

3. The method of claim 1, wherein administering said vector increases serum insulin levels in said mammal.

4. The method of claim 1, wherein the mammal is a rodent or human.

5. The method of claim 1, wherein the mammal is further administered a transfection agent.

6. The method of claim 1, wherein the administering is by intravenous delivery.

7. A method of inducing a pancreatic islet gene expression profile in a liver cell of a subject, said method comprising administering to a subject an adenoviral particle comprising an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide in an amount sufficient to induce said pancreatic islet gene expression in said liver cell in said subject.

8. A method of inducing insulin expression in the liver of a mammal, said method comprising administering to a mammal an adenoviral particle comprising an adenovirus vector comprising a cytomegaloviras (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide in an amount sufficient to induce said insulin expression in said liver of said mammal.

9. A method of inducing glucagon expression in the liver of a mammal, said method comprising administering to a mammal an adenoviral particle comprising an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide in an amount sufficient to induce said glucagon expression in said liver of said mammal.

10. A method of inducing somatostatin expression in the liver of a mammal, said method comprising administering to a mammal an adenoviral particlecomprising an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide in an amount sufficient to induce said somatostatin expression in said liver of said mammal.

11. A method of inducing prohormone convertase 1/3 (PC1/3) expression in the liver of a mammal, said method comprising administering to a mammal an adenoviral particle comprising an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide in an amount sufficient to induce said PC1/3 expression in said liver of said mammal.

12. A method of inducing pancreatic hormone expression in a liver cell, wherein said pancreatic hormone is selected from the group consisting of insulin, somatostatin, and glucagon, said method comprising contacting said cell with an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide, thereby inducing said pancreatic hormone expression in said liver cell.

13. A method of inducing insulin expression in a liver cell, said method comprising contacting said cell with an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide, thereby inducing said insulin expression in said liver cell.

14. A method of inducing somatostatin expression in a liver cell, said method comprising contacting said cell with an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide, thereby inducing said somatostatin expression in said liver cell.

15. A method of inducing glucagon expression in a liver cell, said method comprising contacting said cell with an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide, thereby inducing said glucagon expression in said liver cell.

16. A method of inducing prohormone convertase 1/3 (PC1/3) expression in a liver cell, said method comprising contacting said cell with an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide, thereby inducing said PC1/3 expression in said liver cell.

17. A composition comprising an adenovirus vector comprising a cytomegalovirus (CMV) promoter operably linked to a nucleic acid encoding a pancreatic and duodenal homobox 1 (PDX-1) polypeptide, and a carrier.