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CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy
Hyperornithinemia with gyrate atrophy of the choroid and retina (HOGA) is a severe recessive inherited disease, causing muscular degeneration and retinochoroidal atrophy that progresses to blindness. HOGA arises from mutations in the ornithine aminotransferase (OAT) gene, and nearly one-third of the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248217/ https://www.ncbi.nlm.nih.gov/pubmed/35782600 http://dx.doi.org/10.1016/j.ymgmr.2022.100863 |
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author | Maldonado, Rocio Jalil, Sami Keskinen, Timo Nieminen, Anni I. Hyvönen, Mervi E. Lapatto, Risto Wartiovaara, Kirmo |
author_facet | Maldonado, Rocio Jalil, Sami Keskinen, Timo Nieminen, Anni I. Hyvönen, Mervi E. Lapatto, Risto Wartiovaara, Kirmo |
author_sort | Maldonado, Rocio |
collection | PubMed |
description | Hyperornithinemia with gyrate atrophy of the choroid and retina (HOGA) is a severe recessive inherited disease, causing muscular degeneration and retinochoroidal atrophy that progresses to blindness. HOGA arises from mutations in the ornithine aminotransferase (OAT) gene, and nearly one-third of the known patients worldwide are homozygous for the Finnish founder mutation OAT c.1205 T > C p.(Leu402Pro). We have corrected this loss-of-function OAT mutation in patient-derived induced pluripotent stem cells (iPSCs) using CRISPR/Cas9. The correction restored OAT expression in stem cells and normalized the elevated ornithine levels in cell lysates and cell media. These results show an efficient recovery of OAT function in iPSC, encouraging the possibility of autologous cell therapy for the HOGA disease. |
format | Online Article Text |
id | pubmed-9248217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92482172022-07-02 CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy Maldonado, Rocio Jalil, Sami Keskinen, Timo Nieminen, Anni I. Hyvönen, Mervi E. Lapatto, Risto Wartiovaara, Kirmo Mol Genet Metab Rep Research Paper Hyperornithinemia with gyrate atrophy of the choroid and retina (HOGA) is a severe recessive inherited disease, causing muscular degeneration and retinochoroidal atrophy that progresses to blindness. HOGA arises from mutations in the ornithine aminotransferase (OAT) gene, and nearly one-third of the known patients worldwide are homozygous for the Finnish founder mutation OAT c.1205 T > C p.(Leu402Pro). We have corrected this loss-of-function OAT mutation in patient-derived induced pluripotent stem cells (iPSCs) using CRISPR/Cas9. The correction restored OAT expression in stem cells and normalized the elevated ornithine levels in cell lysates and cell media. These results show an efficient recovery of OAT function in iPSC, encouraging the possibility of autologous cell therapy for the HOGA disease. Elsevier 2022-04-01 /pmc/articles/PMC9248217/ /pubmed/35782600 http://dx.doi.org/10.1016/j.ymgmr.2022.100863 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Maldonado, Rocio Jalil, Sami Keskinen, Timo Nieminen, Anni I. Hyvönen, Mervi E. Lapatto, Risto Wartiovaara, Kirmo CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy |
title | CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy |
title_full | CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy |
title_fullStr | CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy |
title_full_unstemmed | CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy |
title_short | CRISPR correction of the Finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in iPSC from patients with gyrate atrophy |
title_sort | crispr correction of the finnish ornithine delta-aminotransferase mutation restores metabolic homeostasis in ipsc from patients with gyrate atrophy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248217/ https://www.ncbi.nlm.nih.gov/pubmed/35782600 http://dx.doi.org/10.1016/j.ymgmr.2022.100863 |
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