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

Bates, E. A. et al. (2021) In vitro and in vivo evaluation of human adenovirus type 49 as a vector for therapeutic applications. Viruses, 13(8), 1483. (doi: 10.3390/v13081483)

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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-existing 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 relatively 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Nicklin, Professor Stuart and Bradshaw, Dr Angela
Creator Roles:
Bradshaw, A. C.Methodology, Investigation, Formal analysis, Writing – review and editing
Nicklin, S.Investigation, Formal analysis, Writing – review and editing
Nicklin, S. A.Methodology
Baker, A. H.Conceptualization, Methodology, Data curation, Formal analysis, Writing – original draft, Writing – review and editing
Authors: Bates, E. A., Counsell, J. R., Alizert, S., Baker, A. T., Suff, N., Boyle, A., Bradshaw, A. C., Waddington, S. N., Nicklin, S. A., Baker, A. H., and Parker, A. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Viruses
Publisher:MDPI
ISSN:1999-4915
ISSN (Online):1999-4915
Published Online:28 July 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Viruses 13(8): 1483
Publisher Policy:Reproduced under a Creative Commons License

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