Latest Developments in Gene Therapy for Heart Failure

Purpose of Review: To describe the current state of gene transfer therapy for inherited cardiomyopathies, focusing on targets, recent experience, limitations, and challenges. Recent Findings: The use of adeno-associated viral vectors with enhanced cardiac tropism has enabled gene transfer therapy for cardiovascular diseases to advance substantially over the past decade. These vectors are now being used to deliver therapeutic genes that potentially can correct specific genetic mutations associated with heart failure, including those involving genes, such as SERCA2a, BAG3, PKP2, LAMP2, MYBPC3 and FXN, that encode proteins that are critical for normal cell function. Experience from recent clinical trials, however, underlines the need for improved methodologies and safety protocols. Despite recent success, there is a need to address existing challenges related to vector delivery, immune responses, and trial design for the field to advance. Summary: Gene transfer therapies present a promising approach for treating genetic cardiomyopathies. Addressing issues related to vector efficiency, immune reactions and trial design is essential to move the field forward. Future research should be aimed at refining existing gene transfer strategies and clinical trial design with the goal of improving outcomes in patients with genetic cardiomyopathies. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.