Gene therapy for cardiovascular applications

This chapter aims to provide a general overview of the progress made in the gene therapy field to provide the necessary amount of gene expression in various models of cardiovascular disease in order to demonstrate both functional and morphological correction in the heart. The initial viral-based gene delivery experiments were performed in vitro using replication defective retroviral vectors in an attempt to transduce endothelial cells. Preliminary viral-based in vivo cardiovascular gene delivery experiments were also performed using retroviral vectors and demonstrated this vector system's ability to successfully transduce vascular endothelial cells. Other studies have been aimed at demonstrating transduction of the injured myocardium following myocardial infarction. Another viral-based gene delivery system that has been extensively studied is the adenovirus (Ad) vector. Lentivirus-based vectors have also been utilized for cardiovascular gene delivery. Preliminary experiments involved the use of lentivirus for the in vitro delivery of genes into both dividing and nondividing cells in tissue culture. Initial experiments utilizing non-viral-based gene delivery systems often involved simple injections of DNA directly into the myocardium. Investigators have demonstrated vascular gene delivery mediated by polyelectrolyte nanoparticles. This method prevented particle aggregation under physiological conditions and resulted in high transfection efficiency into the rat carotid artery in vivo. Non-viral delivery systems can successfully overcome many of the challenges faced by the viral systems such as viral toxicity, transgene size limitations, and potential for frequent random integration.