Retargeting of adenovirus vectors through genetic fusion of a single-chain or single-domain antibody to capsid protein IX.

Journal of Virology
Kathy L PoulinRobin J Parks

Abstract

Adenovirus (Ad) vectors are the most commonly used system for gene therapy applications, due in part to their ability to infect a wide array of cell types and tissues. However, many therapies would benefit from the ability to target the Ad vector only to specific cells, such as tumor cells for cancer gene therapy. In this study, we investigated the utility of capsid protein IX (pIX) as a platform for the presentation of single-chain variable-fragment antibodies (scFv) and single-domain antibodies (sdAb) for virus retargeting. We show that scFv can be displayed on the capsid through genetic fusion to native pIX but that these molecules fail to retarget the virus, due to improper folding of the scFv. Redirecting expression of the fusion protein to the endoplasmic reticulum (ER) results in correct folding of the scFv and allows it to recognize its epitope; however, ER-targeted pIX-scFv was incorporated into the Ad capsid at a very low level which was not sufficient to retarget virus infection. In contrast, a pIX-sdAb construct was efficiently incorporated into the Ad capsid and enhanced virus infection of cells expressing the targeted receptor. Taken together, our data indicate that pIX is an effective platform for presentation of...Continue Reading

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Citations

Jul 19, 2013·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Benoit B GouletRobin J Parks
Feb 9, 2012·Advances in Virology·M H Verheije, P J M Rottier
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Jun 16, 2018·Cancers·Alexander T BakerAlan L Parker
Aug 24, 2020·Current Problems in Cancer·Nasser Hashemi GoradelBabak Negahdari

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