ADENOASSOCIATED VIRUS-MEDIATED GENE-TRANSFER INTO RAT CAROTID ARTERIES

Gene transfer into the arterial wall may allow study of the role of sp ecific 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 a nd balloon-injured rat carotid arteries was studied using a recombinan t AAV carrying CMVlacZ as a reporter gene. Approximately 10(6) and 10( 7) infectious units (IU) of AV were infused into 1 cm isolated segment s of the carotid artery of 14 animals with the aid of a Silastic cathe ter and allowed to remain for 20 min. Animals were killed at different time-points after infection and arteries stained for beta-gal activit y. 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 o f in vivo beta-gal expression persisted for at least 30 days after gen e transfer. Thus, AAV is capable of transducing media and adventitia o f rat carotid arteries, suggesting that it may constitute a useful vec tor for arterial gene transfer and gene therapy protocols.