In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications.
Viruses
; 13(8)2021 07 28.
Article
in En
| MEDLINE
| ID: mdl-34452348
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Therapy
/
Adenoviruses, Human
/
Genetic Vectors
Type of study:
Evaluation_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Viruses
Year:
2021
Document type:
Article
Affiliation country:
United kingdom