Je. Willard et al., GENETIC-MODIFICATION OF THE VESSEL WALL - COMPARISON OF SURGICAL AND CATHETER-BASED TECHNIQUES FOR DELIVERY OF RECOMBINANT ADENOVIRUS, Circulation, 89(5), 1994, pp. 2190-2197
Background Gene transfer can potentially alter vessel wall biology and
intervene in the pathogenesis of human disease. Although several meth
ods for vector delivery have been described, systematic comparisons of
these methods are unavailable. Therefore, this study compared three c
atheter-based strategies and a surgical technique to assess efficient
and selective gene transfer to the vascular wall. Methods and Results
The common carotid arteries and internal jugular veins of New Zealand
White rabbits were infected with recombinant adenovirus encoding eithe
r firefly luciferase or a nuclear-localizing variant of beta-galactosi
dase. Delivery of recombinant virus was achieved by one of four method
s: (1) instillation within a surgically isolated vessel segment (dwell
), (2) a double-balloon catheter, (3) a perforated balloon catheter (W
olinsky), or (4) an angioplasty balloon catheter coated with a hydroph
ilic adsorbent polymer (Hydrogel). Vessel segments were analyzed 4 day
s after infection for luciferase and beta-galactosidase activity and f
or the extent of injury to the vessel wall. Luciferase activity in ves
sels infected using the double-balloon method was substantially greate
r than that achieved by catheter-based methods (P<.05). The dwell and
double-balloon methods yielded selective expression in intimal cells,
whereas arteries infected using perforated or Hydrogel-coated balloon
catheters demonstrated expression primarily in medial cells. Tissue in
jury was most pronounced with the perforated balloon catheter. Conclus
ions Prototype catheters permit relatively efficient direct gene trans
fer to vascular endothelium; however, delivery methods for targeting t
he medial cells are inefficient. Modifications are needed to optimize
direct gene transfer and minimize tissue injury.