Adenovirus-mediated gene transfer into injured arteries: quantitative analysis of repeated administration

We evaluated quantitatively the efficiency and safety of, and influence of either prior arterial injury or immunity against adenovirus on adenovirus-mediated gene transfer into injured arteries of a relatively large animal model, the dog. A replication-defective adenovirus expressing bacterial lacZ was introduced percutaneously into balloon-injured femoral arteries through a double balloon catheter. After a single dose of adenovirus, up to 90% of surface and smooth muscle cells in multiple layers of the media showed transgene expression evaluated by X-Gal histostaining without extralocal expression, as assessed by the polymerase chain reaction. High level expression measured as beta-galactosidase activity peaked at 7 days after transfer and was transient, though retained for a month. Gene transfer performed just after balloon injury induced submaximal gene expression. A second administration of the same adenovirus to the same arterial site enhanced lacZ expression significantly despite the presence of an immune response. Expression of lacZ was also detected in preimmunized dogs, although the expression levels correlated inversely to the titer of neutralizing antibodies in their serum. These data may provide a scientific foundation for the use of adenovirus-mediated arterial gene transfer in future clinical practice.