Challenges and innovations in cardiac AAV gene delivery as a platform for cardiac regeneration

Gene therapies are at the forefront of potential treatments for cardiovascular diseases, but clinical translation remains limited by poor myocardial access and retention, systemic distribution, and immune-mediated toxicities. Heavily underexplored, the route of administration dictates efficacy and safety, ultimately influencing therapeutic outcomes. This review addresses the role of delivery in overcoming these challenges in cardiac adeno-associated viral therapies. Emphasis is placed on biomaterial-based delivery approaches to improve therapeutic outcomes.