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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2023
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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. |
format | Online Article Text |
id | pubmed-10034418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
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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