Gene transfer to the heart: Emerging strategies for the selection of vectors, delivery techniques, and therapeutic targets

Heart diseases are a major cause of morbidity and mortality in contemporary society. Advances in the understanding of the molecular basis of myocardial dysfunction have placed many acquired and congenital cardiovascular diseases within the reach of gene-based therapy. Four prerequisites are required for a successful clinical application of gene therapy: (1) an effective strategy for genetic manipulation, (2) availability of vectors with enhanced myocardial tropism, (3) a clinically translatable delivery technique that will result in global or regional expression, and (4) creation of therapeutic transgenes for selected molecular targets depending on the underlying pathological state of the heart. Despite significant promise, however, several obstacles exist with gene-based therapies. These obstacles are described in detail in this chapter, along with proposed solutions. We anticipate that advances in the field will improve cardiac gene therapy in future clinical approaches.