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Prime Editing for Inherited Retinal Diseases

Inherited retinal diseases (IRDs) are chronic, hereditary disorders that lead to progressive degeneration of the retina. Disease etiology originates from a genetic mutation—inherited or de novo—with a majority of IRDs resulting from point mutations. Given the plethora of IRDs, to date, mutations tha...

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Autores principales: da Costa, Bruna Lopes, Levi, Sarah R., Eulau, Eric, Tsai, Yi-Ting, Quinn, Peter M. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656220/
https://www.ncbi.nlm.nih.gov/pubmed/34901928
http://dx.doi.org/10.3389/fgeed.2021.775330
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author da Costa, Bruna Lopes
Levi, Sarah R.
Eulau, Eric
Tsai, Yi-Ting
Quinn, Peter M. J.
author_facet da Costa, Bruna Lopes
Levi, Sarah R.
Eulau, Eric
Tsai, Yi-Ting
Quinn, Peter M. J.
author_sort da Costa, Bruna Lopes
collection PubMed
description Inherited retinal diseases (IRDs) are chronic, hereditary disorders that lead to progressive degeneration of the retina. Disease etiology originates from a genetic mutation—inherited or de novo—with a majority of IRDs resulting from point mutations. Given the plethora of IRDs, to date, mutations that cause these dystrophies have been found in approximately 280 genes. However, there is currently only one FDA-approved gene augmentation therapy, Luxturna (voretigene neparvovec-rzyl), available to patients with RPE65-mediated retinitis pigmentosa (RP). Although clinical trials for other genes are underway, these techniques typically involve gene augmentation rather than genome surgery. While gene augmentation therapy delivers a healthy copy of DNA to the cells of the retina, genome surgery uses clustered regularly interspaced short palindromic repeats (CRISPR)-based technology to correct a specific genetic mutation within the endogenous genome sequence. A new technique known as prime editing (PE) applies a CRISPR-based technology that possesses the potential to correct all twelve possible transition and transversion mutations as well as small insertions and deletions. EDIT-101, a CRISPR-based therapy that is currently in clinical trials, uses double-strand breaks and nonhomologous end joining to remove the IVS26 mutation in the CEP290 gene. Preferably, PE does not cause double-strand breaks nor does it require any donor DNA repair template, highlighting its unparalleled efficiency. Instead, PE uses reverse transcriptase and Cas9 nickase to repair mutations in the genome. While this technique is still developing, with several challenges yet to be addressed, it offers promising implications for the future of IRD treatment.
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spelling pubmed-86562202021-12-10 Prime Editing for Inherited Retinal Diseases da Costa, Bruna Lopes Levi, Sarah R. Eulau, Eric Tsai, Yi-Ting Quinn, Peter M. J. Front Genome Ed Genome Editing Inherited retinal diseases (IRDs) are chronic, hereditary disorders that lead to progressive degeneration of the retina. Disease etiology originates from a genetic mutation—inherited or de novo—with a majority of IRDs resulting from point mutations. Given the plethora of IRDs, to date, mutations that cause these dystrophies have been found in approximately 280 genes. However, there is currently only one FDA-approved gene augmentation therapy, Luxturna (voretigene neparvovec-rzyl), available to patients with RPE65-mediated retinitis pigmentosa (RP). Although clinical trials for other genes are underway, these techniques typically involve gene augmentation rather than genome surgery. While gene augmentation therapy delivers a healthy copy of DNA to the cells of the retina, genome surgery uses clustered regularly interspaced short palindromic repeats (CRISPR)-based technology to correct a specific genetic mutation within the endogenous genome sequence. A new technique known as prime editing (PE) applies a CRISPR-based technology that possesses the potential to correct all twelve possible transition and transversion mutations as well as small insertions and deletions. EDIT-101, a CRISPR-based therapy that is currently in clinical trials, uses double-strand breaks and nonhomologous end joining to remove the IVS26 mutation in the CEP290 gene. Preferably, PE does not cause double-strand breaks nor does it require any donor DNA repair template, highlighting its unparalleled efficiency. Instead, PE uses reverse transcriptase and Cas9 nickase to repair mutations in the genome. While this technique is still developing, with several challenges yet to be addressed, it offers promising implications for the future of IRD treatment. Frontiers Media S.A. 2021-11-25 /pmc/articles/PMC8656220/ /pubmed/34901928 http://dx.doi.org/10.3389/fgeed.2021.775330 Text en Copyright © 2021 Costa, Levi, Eulau, Tsai and Quinn. https://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 Genome Editing
da Costa, Bruna Lopes
Levi, Sarah R.
Eulau, Eric
Tsai, Yi-Ting
Quinn, Peter M. J.
Prime Editing for Inherited Retinal Diseases
title Prime Editing for Inherited Retinal Diseases
title_full Prime Editing for Inherited Retinal Diseases
title_fullStr Prime Editing for Inherited Retinal Diseases
title_full_unstemmed Prime Editing for Inherited Retinal Diseases
title_short Prime Editing for Inherited Retinal Diseases
title_sort prime editing for inherited retinal diseases
topic Genome Editing
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656220/
https://www.ncbi.nlm.nih.gov/pubmed/34901928
http://dx.doi.org/10.3389/fgeed.2021.775330
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