Adenoviral Vectors for Cardiovascular Diseases
Noel M. Caplice, Timothy O'Brien, and Robert D. Simari
Cardiovascular diseases affect over 60 million people in the United States, and resulted in over 150 billion dollars in expenses in 1996 (American Heart Association, 1997). As such, the potential for clinical benefits from cardiovascular gene transfer is great and the targets for therapy are numerous. Over the last two decades, the development of gene transfer to treat cardiovascular diseases has progressed from concept to clinical trials. This evolution has been advanced by an increased understanding of the inherent requirements for efficient gene transfer, identification of therapeutic targets and the development of improved vectors. The normal heart and vasculature consist of multiple cell types suitable as targets for gene transfer. In addition, in diseased states, the cellular composition of each tissue is altered quantitatively and qualitatively, increasing the complexity and possibly the difficulty of gene transfer. Adenoviral vectors have several advantages for gene transfer to the cardiovascular system, including the ability to transduce quiescent cells. The use of these vectors has been critical to allow the development of gene transfer in pre-clinical animal models of human disease. However, the requirement for the use of adenoviral vectors to obtain efficient gene transfer in these models of cardiovascular disease has delayed clinical application due to concerns regarding toxicity.