Adenovirus-mediated gene transfer to normal and atherosclerotic arteries: A novel approach

Abstract

Previous studies of gene transfer to blood vessels in vivo have relied on intraluminal, catheter-based methods for delivery of adenoviral and other vectors. In this study, topical application of a replication-deficient adenoviral vector was used as an alternative method of gent transfer to the vessel wall. We administered recombinant adenovirus (1.0 to 1.5 x 1010 pfu/mL) containing the nuclear targeted bacterial β-galactosidase gene topically to arteries in normal and atherosclerotic cynomolgus monkeys. Topical administration was achieved by injection of adenoviral suspension within the periarterial sheath. Segments of femoral and carotid arteries were examined histochemically after staining with 5-bromo-4-chloro-3-indolyl-β- D-galactopyranoside 1 day after treatment with the adenovirus. After topical administration of virus, β-galactosidase activity was observed in ≃20% of cells in the adventitia in both normal and atherosclerotic arteries. There was no detectable β-galactosidase activity in cells of the intima or media. Thus, topical application provides an alternative method for gene transfer to blood vessels in vivo. This approach, which does not require interruption of blood flow and does not disrupt the endothelium, may be useful for studies of vascular biology and perhaps gene therapy in both normal and atherosclerotic vessels.