Polymers for improving the in vivo transduction efficiency of AAV2 vectors.

<h4>Background</h4>Adeno-associated virus has attracted great attention as vehicle for body-wide gene delivery. However, for the successful treatment of a disease such as Duchenne muscular dystrophy infusion of very large amounts of vectors is required. This not only raises questions abo...

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Autores principales:	Gilles Moulay, Sylvie Boutin, Carole Masurier, Daniel Scherman, Antoine Kichler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f1de877734aa451f83ba586ae2ea074a
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spelling	oai:doaj.org-article:f1de877734aa451f83ba586ae2ea074a2021-11-18T07:01:10ZPolymers for improving the in vivo transduction efficiency of AAV2 vectors.1932-620310.1371/journal.pone.0015576https://doaj.org/article/f1de877734aa451f83ba586ae2ea074a2010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21203395/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Adeno-associated virus has attracted great attention as vehicle for body-wide gene delivery. However, for the successful treatment of a disease such as Duchenne muscular dystrophy infusion of very large amounts of vectors is required. This not only raises questions about the technical feasibility of the large scale production but also about the overall safety of the approach. One way to overcome these problems would be to find strategies able to increase the in vivo efficiency.<h4>Methodology</h4>Here, we investigated whether polymers can act as adjuvants to increase the in vivo efficiency of AAV2. Our strategy consisted in the pre-injection of polymers before intravenous administration of mice with AAV2 encoding a murine secreted alkaline phosphatase (mSeAP). The transgene expression, vector biodistribution and tissue transduction were studied by quantification of the mSeAP protein and real time PCR. The injection of polyinosinic acid and polylysine resulted in an increase of plasmatic mSeAP of 2- and 12-fold, respectively. Interestingly, polyinosinic acid pre-injection significantly reduced the neutralizing antibody titer raised against AAV2.<h4>Conclusions</h4>Our results show that the pre-injection of polymers can improve the overall transduction efficiency of systemically administered AAV2 and reduce the humoral response against the capsid proteins.Gilles MoulaySylvie BoutinCarole MasurierDaniel SchermanAntoine KichlerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15576 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gilles Moulay Sylvie Boutin Carole Masurier Daniel Scherman Antoine Kichler Polymers for improving the in vivo transduction efficiency of AAV2 vectors.
description	<h4>Background</h4>Adeno-associated virus has attracted great attention as vehicle for body-wide gene delivery. However, for the successful treatment of a disease such as Duchenne muscular dystrophy infusion of very large amounts of vectors is required. This not only raises questions about the technical feasibility of the large scale production but also about the overall safety of the approach. One way to overcome these problems would be to find strategies able to increase the in vivo efficiency.<h4>Methodology</h4>Here, we investigated whether polymers can act as adjuvants to increase the in vivo efficiency of AAV2. Our strategy consisted in the pre-injection of polymers before intravenous administration of mice with AAV2 encoding a murine secreted alkaline phosphatase (mSeAP). The transgene expression, vector biodistribution and tissue transduction were studied by quantification of the mSeAP protein and real time PCR. The injection of polyinosinic acid and polylysine resulted in an increase of plasmatic mSeAP of 2- and 12-fold, respectively. Interestingly, polyinosinic acid pre-injection significantly reduced the neutralizing antibody titer raised against AAV2.<h4>Conclusions</h4>Our results show that the pre-injection of polymers can improve the overall transduction efficiency of systemically administered AAV2 and reduce the humoral response against the capsid proteins.
format	article
author	Gilles Moulay Sylvie Boutin Carole Masurier Daniel Scherman Antoine Kichler
author_facet	Gilles Moulay Sylvie Boutin Carole Masurier Daniel Scherman Antoine Kichler
author_sort	Gilles Moulay
title	Polymers for improving the in vivo transduction efficiency of AAV2 vectors.
title_short	Polymers for improving the in vivo transduction efficiency of AAV2 vectors.
title_full	Polymers for improving the in vivo transduction efficiency of AAV2 vectors.
title_fullStr	Polymers for improving the in vivo transduction efficiency of AAV2 vectors.
title_full_unstemmed	Polymers for improving the in vivo transduction efficiency of AAV2 vectors.
title_sort	polymers for improving the in vivo transduction efficiency of aav2 vectors.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/f1de877734aa451f83ba586ae2ea074a
work_keys_str_mv	AT gillesmoulay polymersforimprovingtheinvivotransductionefficiencyofaav2vectors AT sylvieboutin polymersforimprovingtheinvivotransductionefficiencyofaav2vectors AT carolemasurier polymersforimprovingtheinvivotransductionefficiencyofaav2vectors AT danielscherman polymersforimprovingtheinvivotransductionefficiencyofaav2vectors AT antoinekichler polymersforimprovingtheinvivotransductionefficiencyofaav2vectors
_version_	1718424078179631104

Polymers for improving the in vivo transduction efficiency of AAV2 vectors.

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