[Safety of direct gene transfer into rat carotid arteries mediated by adenoviral vector]

To evaluate the safety of direct gene transfer into rat carotid arteries mediated by adenoviral vector.

After being soaked in high concentration of glucose solution containing Adv5-CMV (control group) or Adv5-CMV/LacZ (treatment group) for 30 minutes, soluble stents were inserted into the lumina of rat carotid arteries and end-to-end anastomoses of cut rat carotid were performed with standard microvascular surgical technique. On the 7th day after surgery, anastomotic carotid arteries of the two groups were obtained, and samples of ascending aortas, hearts, brains, livers, lungs, spleens and kidneys of the treatment group were taken for assessing beta-galactosidase activity and histochemical staining.

Beta-galactosidase activity was not detected in the carotid arteries in the control group and in those organs not directly exposed to adenoviral vector in the treatment group. The amount of beta-galactosidase expression in the carotid arteries in the treatment group was 10.1 x 10(-3) IU/g tissue. Microscopic examination of sections from vessels in the control group and from the aorta, heart, brain, liver, lung, spleen or kidney in the treatment group revealed no X-gal staining. Microscopic examination of the carotid arteries in the treatment group revealed blue-staining in all anastomotic arteries and in all layers of the arterial wall, including the intima, media, and adventitia.

A recombinant gene could be safely delivered to a local site of the vessel by means of infection with adenoviral vector.