Consideration of clinical translation of cardiac AAV gene therapy

Advancements in conventional cardiac care have significantly reduced mortality from coronary heart disease and acute myocardial infarction. However, the prevalence of heart failure continues to increase in an aging population with profound social and economic consequences. Cardiac gene therapy with adeno-associated virus (AAV) vectors is emerging as a potential modality for addressing this desperate clinical need. After showing initial promise in extensive preclinical studies and an early clinical trial, disappointing results of large-scale clinical trial derailed the progress of AAV-mediated cardiac gene therapy. However, it appears that knowledge gained from previous failures coupled with developments in targeted gene delivery have set the stage for a new frontier in cardiac AAV gene therapy.