Biocompatibility of cardiovascular gene delivery catheters with adenovirus vectors: an important determinant of the efficiency of cardiovascular gene transfer.
Gene therapy approaches hold promise for the treatment of a wide variety of cardiovascular diseases. Many strategies for cardiovascular gene therapy involve catheter-mediated vector delivery via intramyocardial injection, intracoronary infusion, or direct gene transfer into the vessel wall. Several different gene delivery catheters have been developed and utilized in preclinical and clinical studies of cardiovascular gene therapy. However, rigorous studies of the biocompatibility of these catheters with gene therapy vectors have not yet been reported. In this report, we have examined the compatibility of cardiovascular gene therapy catheters and catheter constituents with first-generation E1/E3-deleted adenovirus vectors. We show that (i) currently available catheters rapidly and efficiently inactivate adenovirus vector infectivity; (ii) this inactivation is mediated by a variety of commonly used catheter constituents including stainless steel, nitinol, and polycarbonate; (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 compatible with current adenovirus vectors. These results underscore the importance of catheter/vector compatibility and suggest methods for increasing the efficiency of catheter-mediated cardiovascular gene therapy.
Harvard School of Public Health, Boston, Massachusetts 02115, USA.
D J
DJ
Marshall
M
M
Palasis
J J
JJ
Lepore
J M
JM
Leiden
D000256:Adenoviridae / Q000502:physiology*; D000497:Alloys; D001672:Biocompatible Materials; D002319:Cardiovascular System / Q000821:virology; D002404:Catheterization / Q000295:instrumentation*; D003673:Defective Viruses; D015316:Genetic Therapy; D005822:Genetic Vectors; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D008422:Materials Testing; D012709:Serum Albumin / Q000378:metabolism; D013193:Stainless Steel; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000378:metabolism
D000497:Alloys; D001672:Biocompatible Materials; D012709:Serum Albumin; D013193:Stainless Steel; C013616:nitinol; D001616:beta-Galactosidase