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Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients

Inherited retinal dystrophies comprise a broad group of genetic eye diseases without effective treatment. Among them, Stargardt disease is the second most prevalent pathology. This pathology triggers progressive retinal degeneration and vision loss in children and adults. In recent years, the evolut...

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Autores principales: Siles, Laura, Ruiz-Nogales, Sheila, Navinés-Ferrer, Arnau, Méndez-Vendrell, Pilar, Pomares, Esther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034418/
https://www.ncbi.nlm.nih.gov/pubmed/36969552
http://dx.doi.org/10.1016/j.omtn.2023.02.032
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author Siles, Laura
Ruiz-Nogales, Sheila
Navinés-Ferrer, Arnau
Méndez-Vendrell, Pilar
Pomares, Esther
author_facet Siles, Laura
Ruiz-Nogales, Sheila
Navinés-Ferrer, Arnau
Méndez-Vendrell, Pilar
Pomares, Esther
author_sort Siles, Laura
collection PubMed
description Inherited retinal dystrophies comprise a broad group of genetic eye diseases without effective treatment. Among them, Stargardt disease is the second most prevalent pathology. This pathology triggers progressive retinal degeneration and vision loss in children and adults. In recent years, the evolution of several genome editing technologies, such as the CRISPR-Cas9 system, has revolutionized disease modeling and personalized medicine. Human induced pluripotent stem cells also provide a valuable tool for in vitro disease studies and therapeutic applications. Here, we show precise correction of two ABCA4 pathogenic variants in human induced pluripotent stem cells from two unrelated patients affected with Stargardt disease. Gene editing was achieved with no detectable off-target genomic alterations, demonstrating efficient ABCA4 gene correction without deleterious effects. These results will contribute to the development of emerging gene and cell therapies for inherited retinal dystrophies.
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spelling pubmed-100344182023-03-24 Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients Siles, Laura Ruiz-Nogales, Sheila Navinés-Ferrer, Arnau Méndez-Vendrell, Pilar Pomares, Esther Mol Ther Nucleic Acids Original Article Inherited retinal dystrophies comprise a broad group of genetic eye diseases without effective treatment. Among them, Stargardt disease is the second most prevalent pathology. This pathology triggers progressive retinal degeneration and vision loss in children and adults. In recent years, the evolution of several genome editing technologies, such as the CRISPR-Cas9 system, has revolutionized disease modeling and personalized medicine. Human induced pluripotent stem cells also provide a valuable tool for in vitro disease studies and therapeutic applications. Here, we show precise correction of two ABCA4 pathogenic variants in human induced pluripotent stem cells from two unrelated patients affected with Stargardt disease. Gene editing was achieved with no detectable off-target genomic alterations, demonstrating efficient ABCA4 gene correction without deleterious effects. These results will contribute to the development of emerging gene and cell therapies for inherited retinal dystrophies. American Society of Gene & Cell Therapy 2023-03-03 /pmc/articles/PMC10034418/ /pubmed/36969552 http://dx.doi.org/10.1016/j.omtn.2023.02.032 Text en © 2023 The Authors https://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 Original Article
Siles, Laura
Ruiz-Nogales, Sheila
Navinés-Ferrer, Arnau
Méndez-Vendrell, Pilar
Pomares, Esther
Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients
title Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients
title_full Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients
title_fullStr Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients
title_full_unstemmed Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients
title_short Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients
title_sort efficient correction of abca4 variants by crispr-cas9 in hipscs derived from stargardt disease patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034418/
https://www.ncbi.nlm.nih.gov/pubmed/36969552
http://dx.doi.org/10.1016/j.omtn.2023.02.032
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