CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells
| العنوان: | CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells |
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| المؤلفون: | Ciaran M. Lee, Gang Bao, C. S. Bauer, M. Garcia-Lloret, Ayal Hendel, Adam Sheikali, Rosa Bacchetta, Ami J. Shah, Federica Barzaghi, Alice Bertaina, S. Shipp, Maria Grazia Roncarolo, L. Froessl, Mara Pavel-Dinu, Matt Porteus, U. Lakshmanan, Mansi Narula, Esmond Lee, Holly K. Miller, Manish J. Butte, Marianne Goodwin, Laura Passerini |
| المصدر: | Science advances, vol 6, iss 19 Science Advances |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | T-Lymphocytes, Regenerative Medicine, medicine.disease_cause, T-Lymphocytes, Regulatory, 0302 clinical medicine, Genome editing, 2.1 Biological and endogenous factors, CRISPR, Aetiology, Child, Research Articles, Pediatric, Gene Editing, 0303 health sciences, Multidisciplinary, Effector, Gene correction, SciAdv r-articles, FOXP3, Forkhead Transcription Factors, Genetic Diseases, X-Linked, Regulatory, Haematopoiesis, Phenotype, Genetic Diseases, 030220 oncology & carcinogenesis, IPEX syndrome, Development of treatments and therapeutic interventions, Biotechnology, Research Article, Immune regulation, Immunology, Biology, Autoimmune Disease, 03 medical and health sciences, Rare Diseases, Genetics, medicine, Humans, Gene, 030304 developmental biology, 5.2 Cellular and gene therapies, Inflammatory and immune system, X-Linked, Immune dysregulation, Stem Cell Research, medicine.disease, Mutation, Cancer research, Forkhead box protein 3 gene |
| الوصف: | Gene editing of FOXP3 ensures regulated expression and restored function in T cells, supporting clinical applicability. The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases. |
| وصف الملف: | application/pdf |
| تدمد: | 2375-2548 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4aba5971fe26bda15f359faefd78db95Test https://doi.org/10.1126/sciadv.aaz0571Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4aba5971fe26bda15f359faefd78db95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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