Genetic targeting of adenovirus vectors using a reovirus sigma1-based attachment protein

Molecular Therapy : the Journal of the American Society of Gene Therapy
Frederik H E SchagenV W van Beusechem

Abstract

Targeting adenovirus vectors (AdV's) for selective transduction of specific cell types requires ablation of native adenovirus tropism and introduction of a unique target-binding moiety. To bring these requirements within reach, we developed a novel strategy to target AdV's genetically that relies on replacement of the entire adenovirus fiber protein with a fusion molecule comprising the virion-anchoring domain of fiber and the oligomerization domain of reovirus attachment protein sigma1. The chimeric molecule forms trimers, is transported to the nucleus, and assembles onto the adenovirus capsid. In contrast to previously reported genetically targeted vectors, the AdV presented herein propagates efficiently without a requirement for complementing fiber. Due to ablation of the native adenovirus tropism, the infectivity of this AdV was at least 35-fold reduced on 293 cells. Importantly, a His tag incorporated into the chimeric attachment protein conferred His-tag-dependent tropism to the AdV, which resulted in a 12- to 40-fold greater transduction efficiency on two different cell lines expressing a His-tag-binding receptor. In addition, the infection efficiency was strongly reduced by preincubation with a His-tag-specific Ab. Thus...Continue Reading

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Citations

Aug 22, 2014·Human Gene Therapy·Zineb BelcaidRob C Hoeben
Jul 16, 2010·Journal of Virology·Natalya BelousovaVictor Krasnykh
Sep 29, 2009·Biotechnology Letters·Yue-Jun FuAi-Hua Liang
Mar 24, 2007·Trends in Molecular Medicine·Ricardo J M G E BrandwijkVictor L J L Thijssen
May 19, 2009·Advanced Drug Delivery Reviews·Memy H HassanAyman Al-Hendy
Feb 13, 2016·Reproductive Sciences·Essam R OthmanAyman Al-Hendy
Aug 28, 2007·The Journal of Gene Medicine·Ellen A M Schenk-BraatRob C Hoeben
Jan 10, 2012·The Journal of Gene Medicine·Basav N HangalapuraTanja D de Gruijl

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