Stent-based Delivery of Adeno-associated Viral Vectors with Sustained Vascular Transduction and INOS-mediated Inhibition of In-stent Restenosis

Overview

Journal Gene Ther

Date 2017 Aug 24

PMID 28832561

Citations 13

Authors

I Fishbein

D T Guerrero

I S Alferiev

J B Foster

N G Minutolo

M Chorny

A M Monteys

K H Driesbaugh

C Nagaswami

R J Levy

Affiliations

Soon will be listed here.

Abstract

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 AAV2, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2 in the rat carotid artery model of stent angioplasty.

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