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Article

In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications

1
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
2
Genetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
3
NIHR Great Ormond Street Hospital Biomedical Research Centre, 30 Guilford Street, London WC1N 1EH, UK
4
Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK
5
Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ 85259, USA
6
Department of Women and Children’s Health, King’s College London, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK
7
Gene Transfer Technology Group, EGA Institute for Women’s Health, University College London, 86-96 Chenies Mews, London WC1E 6BT, UK
8
MRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witswatersrand, Johannesburg 2193, South Africa
9
Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Glen R. Nemerow
Viruses 2021, 13(8), 1483; https://doi.org/10.3390/v13081483
Received: 5 July 2021 / Revised: 22 July 2021 / Accepted: 26 July 2021 / Published: 28 July 2021
(This article belongs to the Special Issue Adenovirus Cell and Immune Interactions)
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. View Full-Text
Keywords: adenovirus; viral vector; gene therapy; vaccines adenovirus; viral vector; gene therapy; vaccines
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MDPI and ACS Style

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.; Parker, A.L. In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications. Viruses 2021, 13, 1483. https://doi.org/10.3390/v13081483

AMA Style

Bates EA, Counsell JR, Alizert S, Baker AT, Suff N, Boyle A, Bradshaw AC, Waddington SN, Nicklin SA, Baker AH, Parker AL. In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications. Viruses. 2021; 13(8):1483. https://doi.org/10.3390/v13081483

Chicago/Turabian Style

Bates, Emily A., John R. Counsell, Sophie Alizert, Alexander T. Baker, Natalie Suff, Ashley Boyle, Angela C. Bradshaw, Simon N. Waddington, Stuart A. Nicklin, Andrew H. Baker, and Alan L. Parker. 2021. "In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications" Viruses 13, no. 8: 1483. https://doi.org/10.3390/v13081483

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