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Issue 4, 2020
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Chemical modification of the adeno-associated virus capsid to improve gene delivery

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Abstract

Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells and sustained maintenance of the viral genome. However, the conclusion from clinical data using these vectors is that there is a need to develop new AAVs with a higher transduction efficiency and specificity for relevant target tissues. To overcome these limitations, we chemically modified the surface of the capsid of AAV vectors. These modifications were achieved by chemical coupling of a ligand by the formation of a thiourea functionality between the amino group of the capsid proteins and the reactive isothiocyanate motif incorporated into the ligand. This strategy does not require genetic engineering of the capsid sequence. The proof of concept was first evidenced using a fluorophore (FITC). Next, we coupled the N-acetylgalactosamine ligand onto the surface of the AAV capsid for asialoglycoprotein receptor-mediated hepatocyte-targeted delivery. Chemically-modified capsids also showed reduced interactions with neutralizing antibodies. Taken together, our findings reveal the possibility of creating a specific engineered platform for targeting AAVs via chemical coupling.

Graphical abstract: Chemical modification of the adeno-associated virus capsid to improve gene delivery

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Supplementary files

Article information


Submitted
21 Aug 2019
Accepted
02 Dec 2019
First published
09 Dec 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 1122-1131
Article type
Edge Article

Chemical modification of the adeno-associated virus capsid to improve gene delivery

M. Mével, M. Bouzelha, A. Leray, S. Pacouret, M. Guilbaud, M. Penaud-Budloo, D. Alvarez-Dorta, L. Dubreil, S. G. Gouin, J. P. Combal, M. Hommel, G. Gonzalez-Aseguinolaza, V. Blouin, P. Moullier, O. Adjali, D. Deniaud and E. Ayuso, Chem. Sci., 2020, 11, 1122
DOI: 10.1039/C9SC04189C

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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