Chimeric Adeno-Associated Virus-Mediated Cardiovascular Reprogramming for Ischemic Heart Disease

So Young Yoo; Su-Nam Jeong; Jeong-In Kang; Seung-Wuk Lee

doi:10.1021/acsomega.8b00904

Chimeric Adeno-Associated Virus-Mediated Cardiovascular Reprogramming for Ischemic Heart Disease

ACS Omega. 2018 May 31;3(5):5918-5925. doi: 10.1021/acsomega.8b00904.

Authors

So Young Yoo^{1

2}, Su-Nam Jeong¹, Jeong-In Kang^{2

3}, Seung-Wuk Lee⁴

Affiliations

¹ BIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, Republic of Korea.
² Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea.
³ Control and Instrumentation Engineering, Korea Maritime and Ocean University, Busan 49112, Republic of Korea.
⁴ Bioengineering, University of California, Berkeley, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

Abstract

Here, we demonstrated chimeric adeno-associated virus (chimeric AAV), AAV-DJ-mediated cardiovascular reprogramming strategy to generate new cardiomyocytes and limit collagen deposition in cardiac fibroblasts by inducing synergism of chimeric AAV-expressing Gata4, Mef2c, Tbx5 (AAV-GMT)-mediated heart reprogramming and chimeric AAV-expressing thymosin β4 (AAV-Tβ4)-mediated heart regeneration. AAV-GMT promoted a gradual increase in expression of cardiac-specific genes, including Actc1, Gja1, Myh6, Ryr2, and cTnT, with a gradual decrease in expression of a fibrosis-specific gene, procollagen type I and here AAV-Tβ4 help to induce GMT expression, providing a chimeric AAV-mediated therapeutic cell reprogramming strategy for ischemic heart diseases.