Abstract 13806: Sendai Virus Vectors Achieve Efficient Integration-Free Cardiac Reprogramming in vitro and in vivo

Direct cardiac reprogramming holds great promise for regenerative medicine. We previously demonstrated that fibroblasts were directly reprogrammed into induced cardiomyocyte-like cells (iCMs) by overexpression of Gata4, Mef2c, and Tbx5 (GMT) using retrovirus vectors. However, these genome-integrating vectors are potentially harmful with inefficient cardiac reprogramming. Here, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors could efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression. SeV-GMT generated 100-fold more beating iCMs than retroviral-GMT and shortened the duration to induce beating cells from 30 to 10 days in mouse fibroblasts. In vivo lineage tracing revealed that the gene transfer of SeV-GMT was more efficient than retroviral-GMT at reprogramming resident cardiac fibroblasts into iCMs in mouse infarct hearts. Moreover, SeV-GMT improved cardiac function and reduced fibrosis after myocardial ...