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dc.creatorMével, M. (Mathieu)-
dc.creatorBouzelha, M. (Mohammed)-
dc.creatorLeray, A. (Aurélien)-
dc.creatorPacouret, S. (Simon)-
dc.creatorGuilbaud, M. (Mickael)-
dc.creatorCombal, J.P. (Jean Philippe)-
dc.creatorHommel, M. (Mirja)-
dc.creatorGouin, S.S. (Sébastien)-
dc.creatorDubreil, L. (Laurence)-
dc.creatorAlvarez-Dorta, D. (Dimitri)-
dc.creatorPenaud-Budloo, M. (Magalie)-
dc.creatorGonzález-Aseguinolaza, G. (Gloria)-
dc.creatorBlouin, V. (Véronique)-
dc.creatorMoullier, P. (Philippe)-
dc.creatorAdjali, O. (Oumeya)-
dc.creatorDeniaud, D. (David)-
dc.creatorAyuso, E. (Eduard)-
dc.identifier.citationMével, M. (Mathieu); Bouzelha, M. (Mohammed); Leray, A. (Aurélien); et al. "Chemical modification of the adeno-associated virus capsid to improve gene delivery". Chemical Science. (4), 2020,es_ES
dc.description.abstractGene 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.es_ES
dc.description.sponsorshipThe authors thank all the staff of the Vector Core at the University Hospital of Nantes (http://umr1089.univ-nantes.fr) for production of the AAV vectors and for technical assistance. We are grateful to Nicolas Jaulin for helping with ow cytometry analysis and Sandy Douthe for her contribution to the quality control of the vector stocks. Analysis and purication of chemical compounds were performed at the Chromatography Platform of CEISAM laboratory – UMR 6230 CNRS/UN, Universit ´e de Nantes. The authors thank the MRic Transmission Electron Microscopy Facility (University of Rennes, CNRS, Inserm, BIOSIT – UMS 3480, US_S 018, F-35000 Rennes, France) for its technical assistance. This research was supported by the Fondation d'Entreprise Th´erapie G´enique en Pays de Loire, the Centre Hospitalier Universitaire (CHU) of Nantes, the Institut National de la Sant´e et de la Recherche M´edicale (INSERM) and the University of Nantes, by a grant from the French National Agency for Research called “Investissements d’Avenir” Equipex Arronax Plus n ANR-11-EQPX-0004 and by Vivet Therapeutics SAS.es_ES
dc.titleChemical modification of the adeno-associated virus capsid to improve gene deliveryes_ES
dc.description.noteThis article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.es_ES
dadun.citation.publicationNameChemical Sciencees_ES

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