IP Library › Granted Patent US 12674177
Granted Patent B2
US 12674177 · App. 17/720,369 · Granted Jul 7, 2026

AAV vectors for vascular gene therapy in coronary heart disease and peripheral ischemia

Inventors: Christian Kupatt (Munich, DE); Rabea Hinkel (Munich, DE)
Assignee: Christian Kupatt
C12N15/86A61K38/18A61K48/005C12N7/00C12N2750/14143
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Quick Facts
Patent No.
US 12674177
App. No.
17/720,369
Granted
Jul 7, 2026
Kind
B2
Abstract

The invention relates to the provision of a gene therapy for coronary heart disease and peripheral ischemia in mammals. One embodiment is an adeno-associated viral vector (AAV vector) comprising a first gene encoding a myocardin-related transcription factor A (MRTF-A). The invention further also relates to a pharmaceutical composition comprising an AAV vector of the invention and a pharmaceutically acceptable carrier. Methods for preparing the vector of the invention are also disclosed.

Claims (17)

1 . A method for inducing neovascularization in ischemic tissue of a mammal diagnosed with coronary heart disease or peripheral ischemia, comprising:

injection an injecting a recombinant adeno-associated viral (AAV) vector comprising a nucleic acid sequence encoding myocardin-related transcription factor A (MRTF-A) into the ischemic tissue such that neovascularization occurs in the ischemic tissue.

2 . The method of claim 1 , wherein the neovascularization in the ischemic tissue comprises increased capillary density and microvascular growth, wherein the microvascular growth occurs concurrently with an increase in pericyte cell recruitment.

3 . The method of claim 1 , wherein the AAV vector is an AAV2/9 vector.

4 . The method of claim 1 , wherein the nucleic acid sequence encoding MRTF-A is operably linked to a myosin light chain 2 (MLC2) promoter, an a myosin heavy chain (α-MHC) promoter, or a troponin (Tnl) promoter.

5 . The method of claim 1 , wherein the coronary heart disease is myocardial ischemia or hibernating myocardium.

6 . The method of claim 1 , wherein the nucleic acid sequence encoding MRTF-A is operably linked to a CMV promoter or a myoblast determination protein 1 (MyoD) promoter.

7 . The method of claim 1 , wherein the expression of MRTF-A in the injected ischemic tissue increases the capillary-to-muscle fiber ratio (c/mf).

8 . The method of claim 1 , wherein the nucleic acid sequence encoding MRTF-A is a human, mouse, rabbit, or pig nucleic acid sequence encoding MRTF-A.

9 . The method of claim 1 , wherein the MRTF-A is a human, mouse, rabbit, or pig MRTF-A.

10 . The method of claim 1 , wherein the injecting the AAV vector is by intravenous injection or intramuscular injection.

11 . A pharmaceutical composition comprising:

a) a pharmaceutically acceptable carrier; and

b) a recombinant adeno-associated virus 2/9 (AAV2/9) vector comprising a nucleic acid sequence encoding MRTF-A operably linked to a promoter.

12 . The pharmaceutical composition of claim 11 , wherein the promoter is a myosin light chain 2 (MLC2) promoter, an a myosin heavy chain (α-MHC) promoter, or a troponin (Tnl) promoter.

13 . The pharmaceutical composition of claim 11 , wherein the promoter is a CMV promoter or a myoblast determination protein 1 (MyoD) promoter.

14 . The pharmaceutical composition of claim 11 , wherein the nucleic acid sequence encoding MRTF-A is a human, mouse, rabbit, or pig nucleic acid sequence encoding MRTF-A.