Anti-DNA antibody modified coronary stent for plasmid gene delivery: results obtained from a porcine coronary stent model.
BACKGROUND
Previous work in our laboratory has demonstrated that the anti-DNA antibody-immobilized stent results in highly site-specific gene delivery in a rabbit carotid model. As a result of the similarity in the anatomy and physiology of the pig and human cardiovascular systems, the porcine coronary stent model was used in the present study to evaluate the site-specificity, efficiency and long-term therapeutic effect of this gene delivery system in pig coronary arteries.


METHODS
A reporter plasmid pEGFP (pEGFP-C1) was tethered on the antibody-immobilized stents and assessed for site-specificity and efficiency in a pig coronary stent model. Inducible nitric oxide synthase (NOS) cDNA (pcDNA3.1-iNOS) was tethered on the stent as a therapeutic gene to evaluate the site-specificity and long-term therapeutic effect of this novel gene delivery system for the inhibition of restenosis after coronary stenting for 28 days.


RESULTS
Both the pEGFP-C1 and pcDNA3.1-iNOS tethered stents achieved site-specific gene transfection without distal spreading in the porcine coronary model. The overall GFP transfection efficiency was 2.6 ± 0.9% of the total cells, whereas the neointimal transfection was more than 6%. Histology and morphology studies showed no significant artery stenosis and intimal proliferation for 28 days after coronary stenting using pcDNA3.1-iNOS tethered stents.


CONCLUSIONS
For the first time, we report the successful use of anti-DNA antibody-immobilized stent as plasmid gene delivery system that possess high efficiency and site-specificity in a porcine coronary stent model. The novel system showed long-term therapeutic effects on the inhibition of restenosis when pcDNA3.1-iNOS was tethered on the stent.
Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, China.
Lin-Hua
LH
Zhang
Tong
T
Luo
Chao
C
Zhang
Peng
P
Luo
Xu
X
Jin
Cun-Xian
CX
Song
Run-Lin
RL
Gao
D000704:Analysis of Variance; D000818:Animals; D000974:Antibodies, Antinuclear / Q000737:chemistry / Q000276:immunology*; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D008297:Male; D023421:Models, Animal; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection
D000974:Antibodies, Antinuclear; D049452:Green Fluorescent Proteins; D052247:Nitric Oxide Synthase Type II