The use of adeno-associated virus (AAV) as an efficient, cardiotropic, and safe vector, coupled with the identification of key molecular targets, has placed gene-based therapies within reach of cardiovascular diseases. The purpose of this review is to provide a focused update on the current advances related to AAV-mediated gene therapy in cardiovascular diseases, and particularly in heart failure (HF), wherein gene therapy has recently made important progress.
Multiple successful preclinical studies suggest a potential utility of AAV gene therapy for arrhythmias and biological heart pacing, as well as RNA overexpression. Moreover, AAV-mediated overexpression of several molecular targets involved in HF has demonstrated promising results in clinically relevant large animal models. In humans, a safe and successful completion of a phase 2 clinical trial targeting the sarcoplasmic reticulum calcium ATPase pump with AAV has been reported. Serial studies are ongoing to further prove the efficacy of AAV-mediated sarcoplasmic reticulum calcium ATPase pump gene transfer in human HF.
Significant progress in clinical translation of AAV-mediated cardiac gene therapy has been achieved in recent years. This will prompt further clinical trials, and positive results could open a new era for cardiac gene therapy.
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Correspondence to Roger J. Hajjar, Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1030, New York, NY 10029, USA. Tel: +1 212 241 8374; fax: +1 212 241 4080; e-mail: firstname.lastname@example.org