Cardiac Gene Therapy

Guillaume Bonnet M.D., Kiyotake Ishikawa M.D., Roger J. Hajjar, Yoshiaki Kawase, Guillaume Bonnet, Kiyotake Ishikawa

Kiyotake Ishikawa

Gene therapy holds great promise as a targeted treatment of cardiovascular diseases, which remain a major cause of morbidity and mortality in contemporary societies. Selection of the appropriate vector delivery method is critical for efficient transduction in the myocardium. Direct myocardial delivery is a feasible and effective method that has been shown to exhibit enhanced gene expression compared to coronary infusion and pericardial delivery. It is one of the most widely used gene transfer methods in both animal studies and clinical trials. The advantages, which result from a delivery that avoids exposure to the blood and bypasses the endothelial barrier, are a high local concentration at the injection site and a decreased leakage to off-target organs. The vectors are injected either with an endomyocardial or an epicardial approach, either surgically or percutaneously. In this chapter, we present the different approaches of direct myocardial injection, their advantages and their realization method in preclinical large animal models of cardiovascular diseases.