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In vitro and in vivo evaluation of human adenovirus type 49 as a vector for therapeutic applications

Bates, EA; Counsell, JR; Alizert, S; Baker, AT; Suff, N; Boyle, A; Bradshaw, AC; ... Parker, AL; + view all (2021) In vitro and in vivo evaluation of human adenovirus type 49 as a vector for therapeutic applications. Viruses , 13 (8) , Article 1483. 10.3390/v13081483. Green open access

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Abstract

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-exist-ing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile— remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a rela-tively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications.

Type: Article
Title: In vitro and in vivo evaluation of human adenovirus type 49 as a vector for therapeutic applications
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/v13081483
Publisher version: https://doi.org/10.3390/v13081483
Language: English
Additional information: © 2021 MDPI. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: adenovirus; viral vector; gene therapy; vaccines
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10132809
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