Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis.
Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis.
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DOI:
10.1038/gt.2017.82
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发表时间:
2017-11
期刊:
影响因子:
5.1
通讯作者:
Levy RJ
中科院分区:
文献类型:
--
作者:
Fishbein I;Guerrero DT;Alferiev IS;Foster JB;Minutolo NG;Chorny M;Monteys AM;Driesbaugh KH;Nagaswami C;Levy RJ
In-stent restenosis remains an important clinical problem in the era of drug eluting stents. Development of clinical gene therapy protocols for the prevention and treatment of in-stent restenosis is hampered by the lack of adequate local delivery systems. Herein we describe a novel stent-based gene delivery platform capable of providing local arterial gene transfer with adeno-associated viral (AAV) vectors. This system exploits the natural affinity of protein G (PrG) to bind to the Fc region of mammalian IgG, making PrG a universal adaptor for surface immobilization of vector-capturing antibodies (Ab). Our results: 1) demonstrate the feasibility of reversible immobilization of AAV2 vectors using vector tethering by AAV2-specific Ab appended to the stent surface through covalently attached PrG, 2) show sustained release kinetics of PrG/Ab-immobilized AAV2 vector particles into simulated physiological medium in vitro and site-specific transduction of cultured cells, 3) provide evidence of long-term (12 weeks) arterial expression of luciferase with PrG/Ab-tethered AAV2Luc, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2iNOS in the rat carotid artery model of stent angioplasty.
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影响因子:
15.3
作者:
Hansson, Goran K.;Geng, Yong-Jian;Holm, Jan;Hardhammar, Peter;Wennmalm, Ake;Jennische, Eva
通讯作者:
Jennische, Eva
DOI:
10.1152/ajpheart.00982.2004
发表时间:
2005-07-01
影响因子:
4.8
作者:
Barbato, JE;Zuckerbraun, BS;Tzeng, E
通讯作者:
Tzeng, E
影响因子:
14
作者:
Fishbein, Ilia;Forbes, Scott P.;Levy, Robert J.
通讯作者:
Levy, Robert J.
影响因子:
10.8
作者:
Ganly, Sandra;Hynes, Sean O.;Greiser, Udo
通讯作者:
Greiser, Udo
影响因子:
4.2
作者:
Ferreira, Valerie;Twisk, Jaap;Gaudet, Daniel
通讯作者:
Gaudet, Daniel