Genetic editing of dysfunctional myocardium

Ongoing advances in vector technology, cardiac gene delivery, and, most importantly, our understanding of HF pathogenesis, encourage consideration of gene therapy for HF at this time. At the present time, strategies that enhance sarcoplasmic calcium transport are supported by substantial evidence in both cardiomyocytes derived from patients with HF and in animal models. In addition, efforts to promote cardiomyocyte survival and function through modulation of antiapoptotic signaling appear quite promising. In ongoing efforts to target cardiac dysfunction, gene transfer provides an important tool to improve our understanding of the relative contribution of specific pathways. Through such experiments, molecular targets can be validated for therapeutic intervention, whether pharmacologic or genetic. Translating these basic investigations into clinical gene therapy for HF, however, remains a formidable challenge. Further development of concepts established in rodent models will be required in large animal models with clinical grade vectors and delivery systems to evaluate both efficacy and safety of these approaches. Nevertheless, practical advances and our growing understanding of the molecular pathogenesis of HF provide reason for cautious optimism.