[A novel anti-DNA antibody modified coronary stent for site-specific plasmid DNA delivery].
OBJECTIVE
To explore the feasibility of using an endovascular metal stent as a highly efficient and site-specific gene delivery system.


METHODS
Stents were formulated with a collagen coating. Anti-DNA monoclonal antibodies were covalently bound to the collagen surface by a cross linking reagent of N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). Binding capacity and stability of antibody and plasmid DNA on stents were quantified by radioactive labeling. The gene transduction efficiency was evaluated in cell culture and in rabbits.


RESULTS
The amount of antibodies binding on collagen matrix through SPDP reaction was 15 times higher than that of through physical absorption (P < 0.005). The binding stability of plasmid was significantly better than the control groups (P < 0.01). There was no harmful effect on cell growth with the anti-DNA antibody modified stents. The stents retrieved from cell culture after 72 hours of incubation in A10 cells showed numerous transducted cells only infiltrating the surface coating indicating a highly localized and efficient gene delivery pattern. Results of in vivo gene transfer by this modified stent revealed (2.8 +/- 0.7)% of total cells transduction and the higher transduction location was neointimal layer (about 7%). No distal spread of vector was detectable in the anti-DNA antibody modified stent implantation animals.


CONCLUSIONS
Anti-DNA antibody modified stents represent a novel highly efficient and site-specific gene delivery system which can deliver various kinds of plasmid vectors. The release of plasmid DNA tethered on the stents could be controlled in some conditions. This novel system provided a novel platform for cardiovascular site-specific gene therapy.
Jin
Xu
X
Key Laboratory of Biomaterials of Tianjin, Institute of Biomedical Engineering, CAMS and PUMC, Tianjin 300192, China.
Leng
Xi-gang
XG
Liu
Lan-xia
LX
Gu
Hai-gang
HG
Zhang
Chao
C
Wang
Hai
H
Song
Cun-xian
CX
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D003094:Collagen; D004247:DNA / Q000235:genetics*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D010957:Plasmids; D011817:Rabbits; D013193:Stainless Steel; D015607:Stents
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D020099:Coated Materials, Biocompatible; D013193:Stainless Steel; D003094:Collagen; D004247:DNA