Delivery strategies for gene therapy of chronic heart failure

Chronic heart failure (CHF) is still the leading cause of morbidity and mortality worldwide, causing a great economic burden to the society. Although conventional therapy has a substantial role in reducing mortality from heart failure, the efficacy of novel pharmacologic agents and surgery in extending the 5-year survival rate is not satisfactory. Therefore, it is necessary to develop new therapies for this disease. Gene therapy was introduced in 1970s with the development of recombinant DNA technology. Thanks to the recent progress in myocardial metabolism research and the application of vector based gene transfer strategies in animal models and humans, gene therapy would probably be an ideal treatment alternative for CHF. Over the last two decades, much research has been done about gene therapy for heart failure with regard to different genes, different signal transduction pathways, and different delivery methods. As a result, gene therapy of advanced heart failure has become possible. The main goal of gene therapy for CHF is to inhibit apoptosis, reduce the undesirable remodeling, and increase the contractility through the most efficient cardiomyocyte transfection. In this paper, we will review various gene transfer technologies in ischemic heart disease and heart failure models, and discuss the advantages and disadvantages of these strategies in vector-mediated cardiac gene delivery, with emphasis put on the cardiac surgery with recirculating delivery system, a high efficiency approach. Key words: Cardiac surgery with recirculating delivery; Gene delivery methods; Gene therapy, Cardiac; Chronic heart failure