Transduction of rabbit saphenous artery: a comparison of naked DNA, liposome complexes, and adenovirus vectors

The methods and efficiency of gene transfer into rabbit saphenous artery were examined in this study. The purpose was to develop an animal model capable of evaluating the use of angiogenic gene therapy to revascularize necrotic bone more rapidly and completely than by surgical implantation of blood vessels alone. The success of transduction using adenovirus vectors, liposome/DNA complexes, and naked DNA was evaluated with delivery to both intra-luminal and adventitial sites. Intra-luminal and adventitial (extra-luminal) application was used for the viral and liposome methods. Naked DNA was evaluated only in the intra-luminal site, based upon previous reports. Relative transduction success was expressed as the percentage of total cells with β-galactosidase activity. A 20-mm length of saphenous artery exposed surgically was targeted for lacZ gene transfer. Two days after transduction, the arteries were harvested and stained with X-gal for β-galactosidase activity. The percentage of endothelial, media and adventitial cells with β-galactosidase activity was determined. Intra-arterial injection of adenovirus vector transduced the largest amount of cells in all three areas of the vessel (endothelium, media and adventitia). The adenovirus vectors when applied to the adventitia only transduced adventitial cells. Following intra-arterial injection of liposome/DNA complexes transduction was detected only in endothelium. Extra-luminal liposome and intra-arterial naked DNA delivery resulted in no detectable gene transfer. Intra-arterial delivery of an adenovirus vector would likely provide optimal gene transfer for possible angiogenic gene therapy.