Direct in vivo programming of endothelial cells and blood vessels using the transcription factor ETV2 gene

Abstract

The present invention relates to directly reprogramming and converting resident non-endothelial cells of a host into endothelial cells in situ, i.e., in the body or tissue to which ETV2 has been injected, using the ETV2 gene or gene product, which includes DNA, RNA, mRNA, ETV2 protein, or protein-containing exosomes. [Solution] This invention provides a method for converting non-endothelial cells into endothelial cells by delivering the ETV2 gene or gene product to the disease site via local injection in various forms such as lentivirus, retrovirus, adenovirus, adeno-associated virus (AAV), and mRNA. The directly reprogrammed and converted endothelial cells are intended to promote vascular regeneration in tissues where blood vessels have been damaged.

Claims

1. A method for converting non-endothelial cells to endothelial cells, comprising administering a nucleic acid or vector encoding the transcription factor ETV2 to a target to convert non-endothelial cells in a tissue into endothelial cells.

2. The method according to claim 1, wherein the nucleic acid is DNA or RNA.

3. The method according to claim 1, wherein the nucleic acid is mRNA.

4. The method according to claim 1, wherein the nucleic acid or vector encoding ETV2 is a recombinant lentivirus, retrovirus, adenovirus, or adeno-associated virus (AAV).

5. A method for converting non-endothelial cells to endothelial cells, comprising administering the ETV2 protein or a functional fragment thereof to a target body or tissue to convert non-endothelial cells in the tissue into endothelial cells.

6. The method according to claim 5, wherein the protein is contained within an exosome or other particulate structure.

7. A method for generating blood vessels in tissue, comprising administering a nucleic acid or vector encoding the transcription factor ETV2 to a target to convert non-endothelial cells in the tissue into endothelial cells and blood vessels.

8. The method according to claim 7, wherein the nucleic acid is DNA or RNA.

9. The method according to claim 7, wherein the nucleic acid is mRNA.

10. The method according to claim 7, wherein the nucleic acid or vector encoding ETV2 is a recombinant lentivirus, retrovirus, adenovirus, or adeno-associated virus (AAV).

11. A method for generating blood vessels in tissue, comprising targeting the ETV2 protein or a functional fragment thereof to convert non-endothelial cells in the tissue into endothelial cells and blood vessels.

12. The method according to claim 11, wherein the protein is contained within an exosome or other particulate structure.

13. A method for promoting vascular regeneration in tissues with damaged blood vessels, comprising administering a nucleic acid or vector encoding the transcription factor ETV2 to a target to convert non-endothelial cells in the tissue into endothelial cells and blood vessels.

14. The method according to claim 13, wherein the nucleic acid is DNA or RNA.

15. The method according to claim 13, wherein the nucleic acid is mRNA.

16. The method according to claim 13, wherein the nucleic acid or vector encoding ETV2 is a recombinant lentivirus, retrovirus, adenovirus, or adeno-associated virus (AAV).

17. A method for promoting vascular regeneration in tissues with damaged blood vessels, comprising targeting and administering the ETV2 protein or a functional fragment thereof to convert non-endothelial cells in the tissue into endothelial cells and blood vessels.

18. The method according to claim 17, wherein the protein is contained within an exosome or other particulate structure.

19. A method for forming neovascularization in tissue, comprising administering a nucleic acid or vector encoding the transcription factor ETV2 to a target to convert non-endothelial cells in the tissue into endothelial cells and blood vessels.

20. The method according to claim 19, wherein the nucleic acid is DNA or RNA.

21. The method according to claim 19, wherein the nucleic acid is mRNA.

22. The method according to claim 19, wherein the nucleic acid or vector encoding ETV2 is a recombinant lentivirus, retrovirus, adenovirus, or adeno-associated virus (AAV).

23. A method for inducing neovascularization in tissue, comprising targeting the ETV2 protein or a functional fragment thereof to convert non-endothelial cells in the tissue into endothelial cells and blood vessels.

24. The method according to claim 23, wherein the protein is contained within an exosome or other particulate structure.

25. A method for treating a disease requiring revascularization, comprising administering a nucleic acid or vector encoding the transcription factor ETV2 to a target to convert non-endothelial cells in tissue into endothelial cells and blood vessels.

26. The method according to claim 25, wherein the nucleic acid is DNA or RNA.

27. The method according to claim 25, wherein the nucleic acid is mRNA.

28. The method according to claim 25, wherein the nucleic acid or vector encoding ETV2 is a recombinant lentivirus, retrovirus, adenovirus, or adeno-associated virus (AAV).

29. The method according to claim 25, wherein the disease requiring revascularization is coronary artery disease, myocardial infarction, heart failure, peripheral artery disease, severe limb ischemia, stroke, diabetic complications, and injury healing.

30. A method for treating diseases requiring revascularization, comprising targeting and administering the ETV2 protein or a functional fragment thereof to convert non-endothelial cells in tissue into endothelial cells and blood vessels.

31. The method according to claim 30, wherein the protein is contained within an exosome or other particulate structure.

32. The method according to claim 30, wherein the disease requiring revascularization is coronary artery disease, myocardial infarction, heart failure, peripheral artery disease, severe limb ischemia, stroke, diabetic complications, and injury healing.

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