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Split otoferlins reunited

Gene therapy for genetic hearing loss is a nascent field with just a handful of studies published to date that demonstrate proof‐of‐concept recovery of auditory function (reviewed in Ahmed et al, 2017; Lustig & Akil, 2018). One challenge that faces the inner ear field, as well as the broader gen...

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Detalles Bibliográficos
Autores principales: Holt, Jeffrey R, Geleoc, Gwenaelle SG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328905/
https://www.ncbi.nlm.nih.gov/pubmed/30573543
http://dx.doi.org/10.15252/emmm.201809995
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author Holt, Jeffrey R
Geleoc, Gwenaelle SG
author_facet Holt, Jeffrey R
Geleoc, Gwenaelle SG
author_sort Holt, Jeffrey R
collection PubMed
description Gene therapy for genetic hearing loss is a nascent field with just a handful of studies published to date that demonstrate proof‐of‐concept recovery of auditory function (reviewed in Ahmed et al, 2017; Lustig & Akil, 2018). One challenge that faces the inner ear field, as well as the broader gene therapy field, is the need to deliver large gene sequences despite the limited genetic capacity (~4.5 kB) of delivery vehicles such as adeno‐associated viral vectors (AAV). In this issue, Al‐Moyed et al have overcome this conundrum by using two AAV vectors to deliver the coding sequence for otoferlin, which is ~6 kB. With dual‐AAV delivery of split otoferlin and a trans‐splicing approach, they demonstrate recombination of full‐length otoferlin in sensory hair cells of the inner ear, enabling partial restoration of auditory function in deaf, otoferlin‐null mice.
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spelling pubmed-63289052019-01-16 Split otoferlins reunited Holt, Jeffrey R Geleoc, Gwenaelle SG EMBO Mol Med News & Views Gene therapy for genetic hearing loss is a nascent field with just a handful of studies published to date that demonstrate proof‐of‐concept recovery of auditory function (reviewed in Ahmed et al, 2017; Lustig & Akil, 2018). One challenge that faces the inner ear field, as well as the broader gene therapy field, is the need to deliver large gene sequences despite the limited genetic capacity (~4.5 kB) of delivery vehicles such as adeno‐associated viral vectors (AAV). In this issue, Al‐Moyed et al have overcome this conundrum by using two AAV vectors to deliver the coding sequence for otoferlin, which is ~6 kB. With dual‐AAV delivery of split otoferlin and a trans‐splicing approach, they demonstrate recombination of full‐length otoferlin in sensory hair cells of the inner ear, enabling partial restoration of auditory function in deaf, otoferlin‐null mice. John Wiley and Sons Inc. 2018-12-20 2019-01 /pmc/articles/PMC6328905/ /pubmed/30573543 http://dx.doi.org/10.15252/emmm.201809995 Text en © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle News & Views
Holt, Jeffrey R
Geleoc, Gwenaelle SG
Split otoferlins reunited
title Split otoferlins reunited
title_full Split otoferlins reunited
title_fullStr Split otoferlins reunited
title_full_unstemmed Split otoferlins reunited
title_short Split otoferlins reunited
title_sort split otoferlins reunited
topic News & Views
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328905/
https://www.ncbi.nlm.nih.gov/pubmed/30573543
http://dx.doi.org/10.15252/emmm.201809995
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