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1. WO1997012050 - METHOD FOR TRANSFERRING GENES TO THE HEART USING AAV VECTORS

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[ EN ]

WHAT IS CLAIMED IS:

1. An AAV-derived vector comprising:
a. AAV sequences consisting essentially of the replication and packaging signals of AAV; and
b. a gene encoding a protein which, when expressed in cardiac muscle cells or vascular endothelial cells, improves cardiac or vascular function.

2. The AAV-derived vector of Claim 1, wherein the gene encodes an enzyme.

3. The AAV-derived vector of Claim 1 , wherein the gene encodes a protein having an activity on one or more components of blood.

4. The AAV-derived vector of Claim 3, wherein the protein is streptokinase, urokinase or tissue plasminogen activator.

5. The AAV-derived vector of Claim 2, wherein the enzyme is superoxide dismutase.

6. The AAV-derived vector of Claim 1 , wherein the gene encodes a protein which is protective to cells under stress.

7. The AAV-derived vector of Claim 6, wherein the protein is a heat shock protein.

8. The AAV-derived vector of Claim 7, wherein the heat shock protein has an apparent molecular weight of approximately 70 kD.

9. The AAV-derived vector of Claim 1 , wherein the gene encodes a growth factor.

10. The AAV-derived vector of Claim 9, wherein the growth factor is platelet derived growth factor, fibroblast growth factor, epidermal growth factor, transforming growth factor or insulin-like growth factor.

11. The AAV-derived vector of Claim 1 , wherein the gene encodes a protein involved in cholesterol metabolism, circulation or accumulation.

12. The AAV-derived vector of Claim 11, wherein the protein is the low density lipoprotein receptor.

13. The AAV-derived vector of Claim 1 , wherein the gene encodes a protein which is involved in angiogenesis.

14. The AAV-derived vector of Claim 1, wherein the gene encodes a polypeptide involved in controlling blood pressure.

15. The AAV-derived vector of Claim 14, wherein the protein is renin, angiotensin, or an enzyme involved in the activation of renin or angiotensin.

16. A method of delivering DNA which is exogenous to both adeno-associated virus and to a mammalian heart or circulatory system target cell which comprises providing an adeno-associated virus-derived vector which has been modified to comprise said exogenous DNA and causing said vector to transduce said cell.

17. The method of Claim 16, wherein the exogenous DNA comprises an expressible gene and said gene is expressed in said target cell either constitutively or under regulatable conditions.

18. The method of Claim 17, wherein the expressible gene encodes a messenger RNA which is antisense with respect to a messenger RNA transcribed from a gene endogenous to said cell.

19. The method of Claim 17, wherein the expressible gene encodes a growth factor.

20. The method of Claim 17, wherein the expressible gene encodes an enzyme which reduces the level of free radicals.

21. The method of Claim 17, wherein the expressible gene encodes thymidine kinase.

22. The method of Claim 16, wherein the vector does not comprise any AAV gene in functional form.

23. The method of Claim 16, wherein the vector retains essentially only the inverted terminal repeats of AAV.

24. The method of Claim 17, wherein the expressible gene comprises a coding sequence and a regulatory sequence operably linked to said coding sequence, whereby, when said regulatory sequence is activated, a messenger RNA transcript is transcribed from said coding sequence.

25. The method of Claim 16, wherein the target cell is a mammalian cell of a mammalian order selected from the group consisting of Primata, Rodenta, Carnivora and Arteriodactyla.

26. The method of Claim 25, wherein the target cell is a human cell.

27. A method of preventing, treating or ameliorating a genetically determined, predisposed, or affected disorder of the heart or vasculature which comprises delivering exogenous DNA, by the method of Claim 16, to cells of the heart or vasculature, said exogenous DNA being chosen so that said delivery will prevent, treat or ameliorate said genetically determined, predisposed, or affected disorder of the heart or vasculature.

28. A method of delivering viral vectors to cells of a mammalian heart, comprising administering said viral vector via a catheter inserted into a peripheral artery and causing said viral vector to transduce said cells.

29. The method of Claim 28, wherein the viral vector comprises DNA which is exogenous to both the virus from which the viral vector is derived and to cells of a mammalian heart.

30. The method of Claim 29, wherein the viral vector is an adeno-associated virus-derived vector.

31. The method of Claim 30, wherein the exogenous DNA comprises an expressible gene and said gene is expressed in said cells of a mammalian heart either constitutively or under regulatable conditions.

32. The method of Claim 31, wherein the expressible gene encodes a messenger RNA which is antisense with respect to a messenger RNA transcribed from a gene endogenous to said cell.

33. The method of Claim 31, wherein the expressible gene encodes a growth factor.

34. The method of Claim 31, wherein the expressible gene encodes an enzyme which reduces the level of free radicals.

35. The method of Claim 31 , wherein the expressible gene encodes thymidine kinase.

36. The method of Claim 30, wherein the vector does not comprise any AAV gene in functional form.

37. The method of Claim 30, wherein the vector retains essentially only the inverted terminal repeats of AAV.

38. The method of Claim 31, wherein the expressible gene comprises a coding sequence and a regulatory sequence operably linked to said coding sequence, whereby, when said regulatory sequence is activated, a messenger RNA transcript is transcribed from said coding sequence.

39. The method of Claim 28, wherein the target cell is a mammalian cell of a mammalian order selected from the group consisting of Primata, Rodenta, Carnivora and Arteriodactyla.

40. The method of Claim 39, wherein the target cell is a human cell.

41. A method of preventing, treating or ameliorating a genetically determined, predisposed, or affected disorder of the heart which comprises delivering exogenous DNA, by the method of Claim 28, to cells of the heart, said exogenous DNA being chosen so that said delivery will prevent, treat or ameliorate said genetically determined, predisposed, or affected disorder of the heart.