Biocompatibility of cardiovascular gene delivery catheters with adenovirusvectors: An important determinant of the efficiency of cardiovascular genetransfer

Gene therapy approaches hold promise for the treatment of a wide variety of cardiovascular diseases. Many strategies for cardiovascular gene therapy I nvolve catheter-mediated vector delivery via intramyocardial injection, int racoronary infusion, or direct gene transfer into the vessel wall. Several different gene delivery catheters have been developed and utilized in precl inical and clinical studies of cardiovascular gene therapy. However, rigoro us studies of the biocompatibility of these catheters with gene therapy vec tors have not yet been reported. In this report, we have examined the compa tibility of cardiovascular gene therapy catheters and catheter constituents with first-generation E1/E3-deleted adenovirus vectors. We show that (i) c urrently available catheters rapidly and efficiently inactivate adenovirus vector infectivity; (ii) this inactivation is mediated by a variety of comm only used catheter constituents including stainless steel, nitinol, and pol ycarbonate; (iii) catheter-mediated inactivation of adenovirus vectors can be prevented by preflushing catheters with solutions of serum albumin; and (iv) it is possible to identify a set of catheter materials that are compat ible with current adenovirus vectors. These results underscore the importan ce of catheter/vector compatibility and suggest methods for increasing the efficiency of catheter-mediated cardiovascular gene therapy.