Development of a targeted gene vector platform based on simian adenovirus serotype 24.

Journal of Virology
Natalya BelousovaVictor Krasnykh

Abstract

Efforts to develop adenovirus vectors suitable for genetic interventions in humans have identified three major limitations of the most frequently used vector prototype, human adenovirus serotype 5 (Ad5). These limitations--widespread preexisting anti-Ad5 immunity in humans, the high rate of transduction of normal nontarget tissues, and the lack of target-specific gene delivery--justify the exploration of other Ad serotypes as vector prototypes. In this paper, we describe the development of an alternative vector platform using simian Ad serotype 24 (sAd24). We found that sAd24 virions formed unstable complexes with blood coagulation factor X and, because of that, transduced the liver and other organs at low levels when administered intravenously. The overall pattern of biodistribution of sAd24 particles was similar, however, to that of Ad5, and the intravenously injected sAd24 was cleared by Kupffer cells, leading to their depletion. We modified the virus's fiber protein to design a Her2-specific derivative of sAd24 capable of infecting target human tumor cells in vitro. In the presence of neutralizing anti-Ad5 antibodies, Her2-mediated infection with targeted sAd24 compared favorably to that with the Ad5-derived vector. When us...Continue Reading

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Citations

Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Birgit DreierAndreas Plückthun
Feb 7, 2014·Human Gene Therapy·Estrella Lopez-GordoRamon Alemany
Apr 9, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Oh-Joon KwonChae-Ok Yun
May 23, 2015·Human Vaccines & Immunotherapeutics·Pascal R A BuijsBernadette G van den Hoogen
Jan 5, 2018·Human Vaccines & Immunotherapeutics·Jingao GuoDongming Zhou
Nov 21, 2014·Journal of Virology·Peter AbbinkDan H Barouch
May 4, 2017·Oncotarget·Tao ChengDongming Zhou

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