Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques

Adeno-associated virus (AAV) vectors are increasingly used as an effective and safe approach to deliver genetic material to the central nervous system (CNS). The AAV9-derived variants, AAV-PHP. B and AAV-PHP.eB, reportedly broadly transduce cells throughout the CNS compared to the original serotype...

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Autores principales:	Marie-Laure Arotcarena, Sandra Dovero, Nathalie Biendon, Nathalie Dutheil, Vincent Planche, Erwan Bezard, Benjamin Dehay
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	adeno-associated virus intrathecal injection CNS non-human primate animal model Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/e4615ce038d8497193f847e32f41368c
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spelling	oai:doaj.org-article:e4615ce038d8497193f847e32f41368c2021-11-15T10:46:10ZPilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques2296-418510.3389/fbioe.2021.762209https://doaj.org/article/e4615ce038d8497193f847e32f41368c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.762209/fullhttps://doaj.org/toc/2296-4185Adeno-associated virus (AAV) vectors are increasingly used as an effective and safe approach to deliver genetic material to the central nervous system (CNS). The AAV9-derived variants, AAV-PHP. B and AAV-PHP.eB, reportedly broadly transduce cells throughout the CNS compared to the original serotype 9, AAV9. As non-human primate data are scarce, we here evaluated the CNS transduction efficiencies after lumbar intrathecal bolus delivery of identical doses of either AAV-PHP. B:CAG-EGFP or AAV-PHP. eB:CAG-EGFP in rhesus macaque monkeys. AAV-PHP.eB achieved a more efficient and widespread CNS transduction compared to AAV-PHP.B. We report a strong neuronal and oligodendroglial tropism for both variants in the putamen and in the hippocampus. This proof-of-concept experiment highlights the potential value of intrathecal infusions of AAV-PHP.eB to distribute genetic material in the CNS with cell-type specificity and introduces a new opportunity to model brain diseases in rhesus macaque monkeys and further develop gene therapies targeting the CNS in humans.Marie-Laure ArotcarenaSandra DoveroNathalie BiendonNathalie DutheilVincent PlancheVincent PlancheErwan BezardBenjamin DehayFrontiers Media S.A.articleadeno-associated virusintrathecal injectionCNSnon-human primateanimal modelBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adeno-associated virus intrathecal injection CNS non-human primate animal model Biotechnology TP248.13-248.65
spellingShingle	adeno-associated virus intrathecal injection CNS non-human primate animal model Biotechnology TP248.13-248.65 Marie-Laure Arotcarena Sandra Dovero Nathalie Biendon Nathalie Dutheil Vincent Planche Vincent Planche Erwan Bezard Benjamin Dehay Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques
description	Adeno-associated virus (AAV) vectors are increasingly used as an effective and safe approach to deliver genetic material to the central nervous system (CNS). The AAV9-derived variants, AAV-PHP. B and AAV-PHP.eB, reportedly broadly transduce cells throughout the CNS compared to the original serotype 9, AAV9. As non-human primate data are scarce, we here evaluated the CNS transduction efficiencies after lumbar intrathecal bolus delivery of identical doses of either AAV-PHP. B:CAG-EGFP or AAV-PHP. eB:CAG-EGFP in rhesus macaque monkeys. AAV-PHP.eB achieved a more efficient and widespread CNS transduction compared to AAV-PHP.B. We report a strong neuronal and oligodendroglial tropism for both variants in the putamen and in the hippocampus. This proof-of-concept experiment highlights the potential value of intrathecal infusions of AAV-PHP.eB to distribute genetic material in the CNS with cell-type specificity and introduces a new opportunity to model brain diseases in rhesus macaque monkeys and further develop gene therapies targeting the CNS in humans.
format	article
author	Marie-Laure Arotcarena Sandra Dovero Nathalie Biendon Nathalie Dutheil Vincent Planche Vincent Planche Erwan Bezard Benjamin Dehay
author_facet	Marie-Laure Arotcarena Sandra Dovero Nathalie Biendon Nathalie Dutheil Vincent Planche Vincent Planche Erwan Bezard Benjamin Dehay
author_sort	Marie-Laure Arotcarena
title	Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques
title_short	Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques
title_full	Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques
title_fullStr	Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques
title_full_unstemmed	Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques
title_sort	pilot study assessing the impact of intrathecal administration of variants aav-php.b and aav-php.eb on brain transduction in adult rhesus macaques
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e4615ce038d8497193f847e32f41368c
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Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques

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