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Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration

Inherited retinal dystrophies (IRDs) are a large and heterogeneous group of degenerative diseases caused by mutations in various genes. Given the favorable anatomical and immunological characteristics of the eye, gene therapy holds great potential for their treatment. Our goal is to validate the pre...

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Autores principales: Vagni, Paola, Perlini, Laura E., Chenais, Naïg A. L., Marchetti, Tommaso, Parrini, Martina, Contestabile, Andrea, Cancedda, Laura, Ghezzi, Diego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748340/
https://www.ncbi.nlm.nih.gov/pubmed/31551698
http://dx.doi.org/10.3389/fnins.2019.00945
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author Vagni, Paola
Perlini, Laura E.
Chenais, Naïg A. L.
Marchetti, Tommaso
Parrini, Martina
Contestabile, Andrea
Cancedda, Laura
Ghezzi, Diego
author_facet Vagni, Paola
Perlini, Laura E.
Chenais, Naïg A. L.
Marchetti, Tommaso
Parrini, Martina
Contestabile, Andrea
Cancedda, Laura
Ghezzi, Diego
author_sort Vagni, Paola
collection PubMed
description Inherited retinal dystrophies (IRDs) are a large and heterogeneous group of degenerative diseases caused by mutations in various genes. Given the favorable anatomical and immunological characteristics of the eye, gene therapy holds great potential for their treatment. Our goal is to validate the preservation of visual functions by viral-free homology directed repair (HDR) in an autosomal recessive loss of function mutation. We used a tailored gene editing system based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) to prevent retinal photoreceptor death in the retinal degeneration 10 (Rd10) mouse model of retinitis pigmentosa. We tested the gene editing tool in vitro and then used in vivo subretinal electroporation to deliver it to one of the retinas of mouse pups at different stages of photoreceptor differentiation. Three months after gene editing, the treated eye exhibited a higher visual acuity compared to the untreated eye. Moreover, we observed preservation of light-evoked responses both in explanted retinas and in the visual cortex of treated animals. Our study validates a CRISPR/Cas9-based therapy as a valuable new approach for the treatment of retinitis pigmentosa caused by autosomal recessive loss-of-function point mutations.
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spelling pubmed-67483402019-09-24 Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration Vagni, Paola Perlini, Laura E. Chenais, Naïg A. L. Marchetti, Tommaso Parrini, Martina Contestabile, Andrea Cancedda, Laura Ghezzi, Diego Front Neurosci Neuroscience Inherited retinal dystrophies (IRDs) are a large and heterogeneous group of degenerative diseases caused by mutations in various genes. Given the favorable anatomical and immunological characteristics of the eye, gene therapy holds great potential for their treatment. Our goal is to validate the preservation of visual functions by viral-free homology directed repair (HDR) in an autosomal recessive loss of function mutation. We used a tailored gene editing system based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) to prevent retinal photoreceptor death in the retinal degeneration 10 (Rd10) mouse model of retinitis pigmentosa. We tested the gene editing tool in vitro and then used in vivo subretinal electroporation to deliver it to one of the retinas of mouse pups at different stages of photoreceptor differentiation. Three months after gene editing, the treated eye exhibited a higher visual acuity compared to the untreated eye. Moreover, we observed preservation of light-evoked responses both in explanted retinas and in the visual cortex of treated animals. Our study validates a CRISPR/Cas9-based therapy as a valuable new approach for the treatment of retinitis pigmentosa caused by autosomal recessive loss-of-function point mutations. Frontiers Media S.A. 2019-09-10 /pmc/articles/PMC6748340/ /pubmed/31551698 http://dx.doi.org/10.3389/fnins.2019.00945 Text en Copyright © 2019 Vagni, Perlini, Chenais, Marchetti, Parrini, Contestabile, Cancedda and Ghezzi. 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) and the copyright owner(s) 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
Vagni, Paola
Perlini, Laura E.
Chenais, Naïg A. L.
Marchetti, Tommaso
Parrini, Martina
Contestabile, Andrea
Cancedda, Laura
Ghezzi, Diego
Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration
title Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration
title_full Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration
title_fullStr Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration
title_full_unstemmed Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration
title_short Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration
title_sort gene editing preserves visual functions in a mouse model of retinal degeneration
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748340/
https://www.ncbi.nlm.nih.gov/pubmed/31551698
http://dx.doi.org/10.3389/fnins.2019.00945
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