Key result
Human adenovirus type 49 (HAdV-D49) vectors showed reduced liver targeting while maintaining transduction of lung and spleen compared to adenovirus type 5 in vivo.
Why the study?
Species D adenoviruses offer potential advantages for gene therapy due to low pre-existing immunity, but basic virology aspects like cellular tropism, receptor usage, and in vivo biodistribution remain unknown.
HAdV-D49 is a robust viral vector platform for ex vivo manipulation of human cells and in vivo applications targeting the lung or spleen while avoiding liver interactions.
HAdV-D49 characterization extends species D adenovirus data for gene therapy vectors; leaves open in vivo biodistribution and clinical translation.
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.
No takes yet. Share an insight, caveat, or question.
Bates et al. (2021) studied this question. Human adenovirus type 49 (HAdV-D49) vs. Adenovirus type 5 was evaluated on Cellular tropism, receptor usage, and in vivo biodistribution profile. Human adenovirus type 49 (HAdV-D49) vectors showed reduced liver targeting while maintaining transduction of lung and spleen compared to adenovirus type 5 in vivo.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: