Gene therapy for atherosclerotic cardiovascular disease: a time for optimism and caution

Cardiovascular disease is the leading cause of death in the Western world, and gene therapy approaches to several cardiovascular disorders have been proposed. One of the major stumbling blocks to be overcome before widespread clinical use of this technology is how to deliver DNA efficiently and safely to cells in vivo. While delivery of DNA alone is inefficient, use of viral vectors may overcome this problem. Adenoviral vectors are most commonly used in cardiovascular gene delivery, but toxicity related to these vectors remains a concern. In addition, duration of gene expression with use of these vectors is limited, which may be advantageous in settings in which transient expression is satisfactory to obtain a therapeutic effect. Gene therapy has been suggested as an approach to multiple conditions, including restenosis after angioplasty, therapeutic neovascularization, and bypass graft restenosis. Phase 1 clinical trials were recently reported. While proof of principle has been established in preclinical animal models, convincing efficacy data in humans do not yet exist. Improvements in vector technology and methods of catheter-mediated vascular gene delivery are needed before widespread clinical application of this therapy.