Baylor College of Medicine

Cornell University

The State University of New York

Megumi Mathison

Vivek Singh

Vivekkumar B Patel

Hongran Wang

Erin Lynn Reineke

Austin J Cooney

Ronald G Crystal

Todd K Rosengart

Robert Gersch

Vivek P Singh

Embodiments of the disclosure include methods and compositions for in situ cardiac cell regeneration, including transdifferentiation of cardiac cells to cardiomyocytes. In particular embodiments, in situ cardiac cell regeneration encompasses delivery of p63 shRNA and one or both of Hand2 and myocardin, and in specific embodiments further includes one or more of Gata4, Mef2c, and Tbx5. In specific aspects of the disclosure, adult cardiac fibroblasts are reprogrammed into cardiomyocytes using viral vectors that harbor p63 shRNA and one or both of the transcription factors Hand2 and myocardin.

p63 inactivation for the treatment of heart failure

Provided is a method of treating coronary artery disease in a mammal, comprising administering to a region of the heart of the mammal (a) a first vector encoding one or more angiogenic proteins which induce vascularization in the heart of the mammal, and (b) a second vector encoding one or more cardio-differentiating transcription factors which induce the production of induced cardiomyocytes (iCM) in the heart of the mammal, whereby the coronary artery disease in the mammal is treated. In a preferred embodiment, the first vector is an adenoviral vector encoding VEGF and the second vector is a lentiviral vector encoding Gata4, Mef2c, and Tbx5 (GMT).

Angiogenic conditioning to enhance cardiac cellular reprogramming of fibroblasts of the infarcted myocardium

Growing community of inventors

Houston, TX, United States of America

Megumi Mathison