Adeno-associated virus-mediated gene transfer into rat carotid arteries

Abstract

Gene transfer into the arterial wall may allow study of the role of specific genes in vascular pathophysiology and development of local gene therapies for vascular disorders. The feasibility of adeno-associated virus (AAV)-mediated gene transfer into isolated segments of normal and balloon-injured rat carotid arteries was studied using a recombinant AAV carrying CMVlacZ as a reporter gene. Approximately 10⁶ and 10⁷ infectious units (IU) of AAV were infused into 1 cm isolated segments of the carotid artery of 14 animals with the aid of a Silastic catheter and allowed to remain for 20 min. Animals were killed at different time-points after infection and arteries stained for β-gal activity. Microscopic examination demonstrated comparable gene transfer into medial and adventitial cells, with significantly higher efficiency of transduction in injured as compared with normal vessels. High levels of in vivo β-gal expression persisted for at least 30 days after gene transfer. Thus, AAV is capable of transducing media and adventitia of rat carotid arteries, suggesting that it may constitute a useful vector for arterial gene transfer and gene therapy protocols.