Gene Dilivery System Based on Antibody Immobilized Coronary Stent for Intravascular Site-Specific Gene Therapy
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    Abstract:

    Aim To evaluate the possibility and efficiency of stent-based gene delivery system using antibody-tethered adenoviral vector. Methods Stents were formulated with a collagen coating.An anti-adenoviral monoclonal antibodies'(Fab)2' were covalently bound to the collagen surface by reactions with a bi-functional cross linker N-succinimidyl 3-(2-pyridyldithio)propionate(SPDP).These antibodies enabled tethering of replication defective adenovirus encoding green fluorescent protein(Ad-GFP).The function of this novel stent based on gene delivery system was evaluated in cell culture and in animal test. Results Gene delivery from stents carrying antibody-tethered Ad-GFP demonstrated efficient,site-specific and highly localized Ad-GFP transduction in cell culture(transduction efficiency was 92.8%±2.5% vs about 10% in control group).In pig coronary artery stent deployment studies,GFP-positive cells were only observed in the site that direct contact with the antibody-tethered Ad-GFP stent.Most of these cells were neointimal smooth muscle cells(transduction efficiency was more than 17% of total cells in neointimal region and the average transduction efficiency was 5.9%±1.1% for the whole section).No distal spread of vector was detectable by polymerase chain reaction. Conclusion Gene delivery system based on antibody immobilized coronary stents provided localized and highly efficient gene delivery for intravascular site-specific gene therapy.

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JIN Xu~,SONG Cun-Xian~,Robert J Levy~,Bruce D Klugherz~,and Suzanne DeFelice~. Gene Dilivery System Based on Antibody Immobilized Coronary Stent for Intravascular Site-Specific Gene Therapy[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2006,14(7):573-576.

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History
  • Received:July 04,2005
  • Revised:May 03,2006
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