Barriers in Heart Failure Gene Therapy and Approaches to Overcome Them

With the growing prevalence and incidence of heart failure worldwide, investigation and development of new therapies to address disease burden are of great urgency. Gene therapy is one promising approach for the management of heart failure, but several barriers currently exclude safe and effi-cient gene delivery to the human heart. These barriers include the anatomical and biological difficulty of specif-ically targeting cardiomyocytes, the vascular endothelium, and immunogenicity against administered vectors and the transgene. We review approaches taken to overcome these barriers with a focus on vector modification, evasion of im-mune responses, and heart-targeted delivery techniques. While various modifications proposed to date show promise in managing some barriers, continued investigation into improvements to existing therapies is required to overcome limitations in transduction efficiency, duration of transgene expression, and immune response.