Telomerase reverse transcriptase-based therapies for treatment of conditions associated with myocardial infarction
The invention provides compositions and methods useful for the treatment and prevention of conditions associated with myocardial infarction.
1. A method of treating a condition associated with myocardial infarction, the method comprising:
administering to a subject in need thereof a non-integrative viral vector comprising a coding sequence for telomerase reverse transcriptase (TERT), wherein the condition associated with myocardial infarction is selected from the group consisting of a myocardial infarction, tissue damage resulting from myocardial infarction, fibrosis of the myocardium resulting from myocardial infarction, and reduced cardiac function resulting from myocardial infarction, and wherein the method results in the transduction of heart cells.
2. The method of claim 1 , wherein the subject has previously suffered a myocardial infarction event.
3. The method of claim 1 , wherein TERT is encoded by a nucleic acid sequence comprising the sequence of SEQ ID NO: 1 or SEQ ID NO: 3.
4. The method of claim 1 , wherein TERT comprises the amino acid sequence of SEQ ID NO:2 or SEQ ID NO: 4.
5. The method of claim 1 , wherein the nucleic acid sequence encoding TERT is operably linked to a regulatory sequence that drives the expression of the coding sequence.
6. The method of claim 1 , wherein the non-integrative viral vector is an adeno-associated virus-based vector.
7. The method of claim 1 , wherein the non-integrative viral vector is an adeno-associated virus-based vector whose capsid is derived from the serotype 9 adeno-associated virus (AAV9).
8. The method of claim 7 , wherein the coding sequence is packaged in the capsid and is flanked at both ends by the internal terminal repeats of the serotype 2 adeno-associated virus.
9. The method of claim 1 , wherein the non-integrative viral vector comprises a regulatory sequence encoding a constitutive promoter.
10. The method of claim 9 , wherein the constitutive promoter is the cytomegalovirus (CMV) promoter.
11. The method of claim 1 , wherein the non-integrative viral vector is administered directly to the cardiac tissue.
12. The method of claim 1 , wherein the non-integrative viral vector is administered within twelve hours, twenty-four hours, thirty-six hours, forty-eight hours, sixty hours, seventy-two hours, or eighty-four hours after the myocardial infarction.