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

Viruses

Natalie Suff¹  Emily A. Bates²  Alexander T. Baker²  Alan L. Parker²  Ashley Boyle³  Simon N. Waddington³  John R. Counsell⁴  Stuart A. Nicklin⁵  Angela C. Bradshaw⁵  Sophie Alizert⁵  Andrew H. Baker⁵ 

[1] Department of Women and Children’s Health, King’s College London, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK;Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK;Gene Transfer Technology Group, EGA Institute for Women’s Health, University College London, 86-96 Chenies Mews, London WC1E 6BT, UK;Genetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK;Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK;

关键词: adenovirus;    viral vector;    gene therapy;    vaccines;   

DOI  :  10.3390/v13081483

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown