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Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice

Systemic delivery of self-complementary (sc) adeno-associated-virus vector of serotype 9 (AAV9) was recently shown to provide robust and widespread gene transfer to the central nervous system (CNS), opening new avenues for practical, and non-invasive gene therapy of neurological diseases. More recen...

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Autores principales: Tanguy, Yannick, Biferi, Maria G., Besse, Aurore, Astord, Stephanie, Cohen-Tannoudji, Mathilde, Marais, Thibaut, Barkats, Martine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516891/
https://www.ncbi.nlm.nih.gov/pubmed/26283910
http://dx.doi.org/10.3389/fnmol.2015.00036
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author Tanguy, Yannick
Biferi, Maria G.
Besse, Aurore
Astord, Stephanie
Cohen-Tannoudji, Mathilde
Marais, Thibaut
Barkats, Martine
author_facet Tanguy, Yannick
Biferi, Maria G.
Besse, Aurore
Astord, Stephanie
Cohen-Tannoudji, Mathilde
Marais, Thibaut
Barkats, Martine
author_sort Tanguy, Yannick
collection PubMed
description Systemic delivery of self-complementary (sc) adeno-associated-virus vector of serotype 9 (AAV9) was recently shown to provide robust and widespread gene transfer to the central nervous system (CNS), opening new avenues for practical, and non-invasive gene therapy of neurological diseases. More recently, AAV of serotype rh10 (AAVrh10) was also found highly efficient to mediate CNS transduction after intravenous administration in mice. However, only a few studies compared AAV9 and AAVrh10 efficiencies, particularly in the spinal cord. In this study, we compared the transduction capabilities of AAV9 and AAVrh10 in the brain, the spinal cord, and the peripheral nervous system (PNS) after intravenous delivery in neonatal mice. As reported in previous studies, AAVrh10 achieved either similar or higher transduction than AAV9 in all the examined brain regions. The superiority of AAVrh10 over AAV9 appeared statistically significant only in the medulla and the cerebellum, but a clear trend was also observed in other structures like the hippocampus or the cortex. In contrast to previous studies, we found that AAVrh10 was more efficient than AAV9 for transduction of the dorsal spinal cord and the lower motor neurons (MNs). However, differences between the two serotypes appeared mainly significant at low dose, and surprisingly, increasing the dose did not improve AAVrh10 distribution in the spinal cord, in contrary to AAV9. Similar dose-related differences between transduction efficiency of the two serotypes were also observed in the sciatic nerve. These findings suggest differences in the transduction mechanisms of these two serotypes, which both hold great promise for gene therapy of neurological diseases.
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spelling pubmed-45168912015-08-17 Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice Tanguy, Yannick Biferi, Maria G. Besse, Aurore Astord, Stephanie Cohen-Tannoudji, Mathilde Marais, Thibaut Barkats, Martine Front Mol Neurosci Neuroscience Systemic delivery of self-complementary (sc) adeno-associated-virus vector of serotype 9 (AAV9) was recently shown to provide robust and widespread gene transfer to the central nervous system (CNS), opening new avenues for practical, and non-invasive gene therapy of neurological diseases. More recently, AAV of serotype rh10 (AAVrh10) was also found highly efficient to mediate CNS transduction after intravenous administration in mice. However, only a few studies compared AAV9 and AAVrh10 efficiencies, particularly in the spinal cord. In this study, we compared the transduction capabilities of AAV9 and AAVrh10 in the brain, the spinal cord, and the peripheral nervous system (PNS) after intravenous delivery in neonatal mice. As reported in previous studies, AAVrh10 achieved either similar or higher transduction than AAV9 in all the examined brain regions. The superiority of AAVrh10 over AAV9 appeared statistically significant only in the medulla and the cerebellum, but a clear trend was also observed in other structures like the hippocampus or the cortex. In contrast to previous studies, we found that AAVrh10 was more efficient than AAV9 for transduction of the dorsal spinal cord and the lower motor neurons (MNs). However, differences between the two serotypes appeared mainly significant at low dose, and surprisingly, increasing the dose did not improve AAVrh10 distribution in the spinal cord, in contrary to AAV9. Similar dose-related differences between transduction efficiency of the two serotypes were also observed in the sciatic nerve. These findings suggest differences in the transduction mechanisms of these two serotypes, which both hold great promise for gene therapy of neurological diseases. Frontiers Media S.A. 2015-07-28 /pmc/articles/PMC4516891/ /pubmed/26283910 http://dx.doi.org/10.3389/fnmol.2015.00036 Text en Copyright © 2015 Tanguy, Biferi, Besse, Astord, Cohen-Tannoudji, Marais and Barkats. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Tanguy, Yannick
Biferi, Maria G.
Besse, Aurore
Astord, Stephanie
Cohen-Tannoudji, Mathilde
Marais, Thibaut
Barkats, Martine
Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice
title Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice
title_full Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice
title_fullStr Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice
title_full_unstemmed Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice
title_short Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice
title_sort systemic aavrh10 provides higher transgene expression than aav9 in the brain and the spinal cord of neonatal mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516891/
https://www.ncbi.nlm.nih.gov/pubmed/26283910
http://dx.doi.org/10.3389/fnmol.2015.00036
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