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Review
. 2020 Jun;594(12):1918-1946.
doi: 10.1002/1873-3468.13731. Epub 2020 Feb 3.

Retargeting adenoviruses for therapeutic applications and vaccines

Michael A Barry  1 , Jeffrey D Rubin  2 , Shao-Chia Lu  2
Affiliations
Review

Retargeting adenoviruses for therapeutic applications and vaccines

Michael A Barry et al. FEBS Lett. 2020 Jun.

Abstract

Adenoviruses (Ads) are robust vectors for therapeutic applications and vaccines, but their use can be limited by differences in their in vitro and in vivo pharmacologies. This review emphasizes that there is not just one Ad, but a whole virome of diverse viruses that can be used as therapeutics. It discusses that true vector targeting involves not only retargeting viruses, but importantly also detargeting the viruses from off-target cells.

Keywords: Ad serotypes; detargeting; gain of function; liver; retargeting; sequestration; serotypes.

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Figures

Figure 1.
Figure 1.. Cryo-Electron Microscopic Structures of Ad26.
A) Full virion structure B) Fiber and penton base. R indicated fiber shaft repeats. RGD indicates arginine-glycine-aspartic acid integrin binding motifs in the penton base. Knob indicates the receptor binding portion of the Ad26 fiber trimer. Receptors bound by these capsomers are shown on the right. Adapted from [33].
Figure 2.
Figure 2.. Schematic of Different Types of Adenovirus Vectors.
RC-Ad = replication-competent Ad. SC-Ad = single-cycle Ad. RD-Ad = replication-defective, E1-deleted Ad. HD-Ad = helper-dependent Ad.
Figure 3.
Figure 3.. Schematic of the Human Adenovirus Virome Palette for Adenovirus Targeting.
Adapted from [100] and showing whole genome difference between species C Ad6 and species D Ad26 described in [107].
Figure 4.
Figure 4.. mRNA Activation after Infection of Human Lung Cells with Species C Ad6 and Species D Ad26.
See main text for further information. Adapted from [107].
Figure 5.
Figure 5.. Schematic of Adenovirus Retargeting and Detargeting Strategies.
See main text for further information.
See this image and copyright information in PMC

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