Recent developments in gene therapy for cardiac disease

Abstract

Cardiovascular disease is the leading cause of death in the US and worldwide. Advances in molecular biology and the human genome project have revealed opportunities for novel strategies for cardiac gene therapy. This review discusses general and specific aspects of gene transfer strategies in cardiac tissues. These include 1) the selection and/or optimization of the vector for gene transfer; 2) the identification of the target gene(s); 3) the use of cardiac-specific promoters; and 4) the use of an appropriate delivery system for administration. Currently, several vectors (e.g., viral and nonviral vectors) have been developed and many target genes have been identified (e.g., VEGF, FGF, β-AR, etc.). Many investigations have provided experimental models for gene delivery systems but the most efficient cardiac gene transfer was obtained from intramyocardial injection or perfusion of explanted myocardium. The data available thus far have suggested favorable immediate effects following gene transfer, but long-term value of cardiac gene therapy has not been proven. Further refinements in appropriate vectors that provide cell or tissue selectivity and long-lasting effects are necessary as well as the development of minimally invasive procedures for gene transfer.