ADENOVIRAL VECTOR-MEDIATED GENE-TRANSFER INTO SHEEP ARTERIES USING A DOUBLE-BALLOON CATHETER

The potential for catheter-based in vivo delivery of genetic material to the arterial wall is incompletely explored. We evaluated the level of recombinant protein production as well as the anatomic distribution and duration of gene expression following adenoviral vector-mediated gene transfer into sheep arteries via a double balloon catheter. Cathe ters were positioned in the carotid or femoral arteries of 20 sheep vi a a combined percutaneous and surgical approach, and virions infused o ver a 30-min period. Three days later, recombinant gene expression was identified in approximately 30% (range 0-80%) of the luminal endothel ial cells within the targeted area of the artery. Persistent recombina nt protein expression was identified histochemically for up to 4 weeks , although the number of positive cells decreased steadily. High level s of both beta-galactosidase (beta-Gal) activity and protein (mean 20 mU and 44 ng per vessel) were measured in vessel extracts 3 days after gene transfer, again decreasing significantly over a 4-week period. T ransgene expression was limited almost entirely to the intima and adve ntitia; adventitial gene transfer occurred virtually exclusively along the vasa vasorum. In comparison to previous studies of catheter-based gene transfer, adenoviral vectors delivered by double balloon cathete r resulted in a particularly high efficiency of endothelial cell gene transfer. The efficiency and amount of recombinant gene expression ach ieved in this study suggest that catheter-based gene delivery may even tually be applicable to the treatment of focal human arterial disease.