Heart diseases cause significant morbidity and mortality in modern society. Molecular causes for many heart diseases are now clearly defined. Gene therapy represents a critical next step in translating these exciting basic science breakthroughs to human patients. A central issue in gene therapy is to effectively deliver therapeutic genetic materials to the target tissues/organs. In this regard, the heart has been considered as a highly challenging target because of the dynamic nature of the physiology and the unique anatomic location. Significant progress has been made over the last few years in heart gene delivery. What initially started as a simple direct plasmid injection to the rodent myocardium has now evolved into advanced chemical and viral vectors, and also clinically approachable delivery methods for whole heart transduction in large animal models and human patients. Despite the proof-of-principle in numerous animal models and encouraging data in several early stage clinical trials, unequivocal success in human patients remains lacking. Apparently, novel strategies are needed to meet the clinical challenge. In this regard, a clear understanding of the current status of heart gene transfer will serve as a good foundation for future development.
In an Education Session of the recent Annual Meeting of American Society of Gene and Cell Therapy, technological advances and the existing obstacles in the field of heart gene delivery were discussed and updated. A collection of reviews from the speakers of this session is presented in this special issue [1-3]. Three core issues in heart gene therapy are covered. Specifically, what kind of vehicle is appropriate to deliver a therapeutic gene to the heart? What are the pros and cons of various heart gene delivery methods? What genes should we use to treat different types of heart failure?
The ultimate driving forces for cardiac gene therapy are the patient needs. Compared with other commonly used modalities (such as heart transplantation), there is still ample growing space regarding the development of heart gene therapy. Significant effort is warranted to deal with concerns related to inadequate gene transfer efficacy, inefficient gene transfer vectors and compromised gene delivery methods. We hope that this collection of reviews will serve as a starting point for the younger generation of physicians and scientists who are interested in this field. We anticipate many pleasant surprises in the next chapter of heart gene therapy. We firmly believe that the long-sought health benefit of heart gene therapy will be realized in the near future.