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Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae

Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investiga...

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Autores principales: Omichi, Ryotaro, Yoshimura, Hidekane, Shibata, Seiji B., Vandenberghe, Luk H., Smith, Richard J.H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270144/
https://www.ncbi.nlm.nih.gov/pubmed/32518805
http://dx.doi.org/10.1016/j.omtm.2020.05.007
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author Omichi, Ryotaro
Yoshimura, Hidekane
Shibata, Seiji B.
Vandenberghe, Luk H.
Smith, Richard J.H.
author_facet Omichi, Ryotaro
Yoshimura, Hidekane
Shibata, Seiji B.
Vandenberghe, Luk H.
Smith, Richard J.H.
author_sort Omichi, Ryotaro
collection PubMed
description Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9, and Anc80L65, and quantitated dual-vector co-transduction rates following co-injection of AAV2 and AAV9 vectors in adult murine cochlea. We used the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced 96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss. Dual AAV2 injection co-transduced 96.9% ± 1.7% of IHCs and 65.6% ± 8.95% of OHCs. Together, RWM+CF-injected single or dual AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells.
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spelling pubmed-72701442020-06-08 Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae Omichi, Ryotaro Yoshimura, Hidekane Shibata, Seiji B. Vandenberghe, Luk H. Smith, Richard J.H. Mol Ther Methods Clin Dev Article Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9, and Anc80L65, and quantitated dual-vector co-transduction rates following co-injection of AAV2 and AAV9 vectors in adult murine cochlea. We used the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced 96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss. Dual AAV2 injection co-transduced 96.9% ± 1.7% of IHCs and 65.6% ± 8.95% of OHCs. Together, RWM+CF-injected single or dual AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells. American Society of Gene & Cell Therapy 2020-05-13 /pmc/articles/PMC7270144/ /pubmed/32518805 http://dx.doi.org/10.1016/j.omtm.2020.05.007 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Omichi, Ryotaro
Yoshimura, Hidekane
Shibata, Seiji B.
Vandenberghe, Luk H.
Smith, Richard J.H.
Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
title Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
title_full Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
title_fullStr Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
title_full_unstemmed Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
title_short Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
title_sort hair cell transduction efficiency of single- and dual-aav serotypes in adult murine cochleae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270144/
https://www.ncbi.nlm.nih.gov/pubmed/32518805
http://dx.doi.org/10.1016/j.omtm.2020.05.007
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