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Efficient in vivo direct conversion of fibroblasts into cardiomyocytes using a nanoparticle-based gene carrier

Chang, Yujung, Lee, Euiyeon, Kim, Junyeop, Kwon, Yoo-Wook, Kwon, Youngeun, Kim, Jongpil
Biomaterials 2019 v.192 pp. 500-509
GATA transcription factors, cardiac output, cardiomyocytes, cytotoxicity, fibroblasts, gene transfer, genes, humans, mice, myocardial infarction, nanocarriers, nanogold, patients, somatic cells
The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems are required to more efficiently and safely induce in vivo reprogramming of iCMs for therapeutic applications in heart injury. In this study, we show that cationic gold nanoparticles (AuNPs) loaded with Gata4, Mef2c, and Tbx5 function as nanocarriers for cardiac reprogramming. The AuNP/GMT/PEI nanocomplexes show high reprogramming efficiency in human and mouse somatic cells with low cytotoxicity and direct conversion into iCMs without integrating factors into the genome. Importantly, AuNP/GMT/PEI nanocomplexes led to efficient in vivo conversion into cardiomyocytes after myocardial infarction (MI), resulting in the effective recovery of cardiac function and scar area. Taken together, these results show that the AuNP/GMT/PEI nanocarrier can be used to develop effective therapeutics for heart regeneration in cardiac disease patients.