[Animal study of intravascular gene therapy based on polyurethane implantable devices].
OBJECTIVE
To explore the feasibility of utilizing two implantable devices made from modified polyurethane films with antibody tethered replication-defective adenoviruses encoding for green fluorescent protein (AdGFP) as gene delivery platforms.


METHODS
Intra-aortic button implants of collagen-coated polyurethane films with antibody tethered AdGFP were sutured into the infrarenal aorta of adult pigs and pulmonary valve leaflet in juvenile sheep was replaced by polyurethane pulmonary valve cusp replacement with antibody-tethered AdGFP. After seven days, the buttons, prosthetic leaflets, and their surrounding tissues were explanted and evaluated for biocompatibility and AdGFP-mediated gene transfer by fluorescent microscopy and PCR analysis.


RESULTS
In vivo analysis of gene transfer from collagen-coated polyurethane films in pig infrarenal aorta implants, one week explants of the collagen-coated polyurethane films demonstrated (14.2 +/- 2.5)% of neointimal cells on the surface of the implant. In sheep pulmonary valve leaflet replacement studies, polyurethane films with antibody tethered AdGFP vector demonstrated (25.1 +/- 5.7)% of cells attached to polyurethane valve leaflets were transduced in one week. PCR analyses showed that GFP DNA was not detectable in blood or distal tissues.


CONCLUSIONS
Site-specific intravascular delivery of adenoviral vectors for gene therapy can be achieved with these two kinds of polyurethane implants utilizing the antivector antibody tethering mechanism.
Song
Cun-xian
CX
Tianjin Biomedical Material Key Laboratory, Institute of Biomedical Engineering, CAMS and PUMC, Tianjin 300192, China. scxian@tom.com
Zhang
Lin-hua
LH
Yang
Jin
J
Stachelek
Stanley J
SJ
Levy
Robert J
RJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001807:Blood Vessel Prosthesis; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006350:Heart Valve Prosthesis; D008297:Male; D011140:Polyurethanes / Q000737:chemistry; D019919:Prosthesis Implantation; D012756:Sheep; D013552:Swine
D011140:Polyurethanes; D049452:Green Fluorescent Proteins