CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells
dc.contributor.author | Goodwin, M. | |
dc.contributor.author | Lee, E. | |
dc.contributor.author | Lakshmanan, U. | |
dc.contributor.author | Shipp, S. | |
dc.contributor.author | Froessl, L. | |
dc.contributor.author | Barzaghi, F. | |
dc.contributor.author | Passerini, L. | |
dc.contributor.author | Narula, M. | |
dc.contributor.author | Sheikali, A. | |
dc.contributor.author | Lee, Ciaran M. | |
dc.contributor.author | Bao, G. | |
dc.contributor.author | Bauer, C. S. | |
dc.contributor.author | Miller, H. K. | |
dc.contributor.author | Garcia-Lloret, M. | |
dc.contributor.author | Butte, M. J. | |
dc.contributor.author | Bertaina, A. | |
dc.contributor.author | Shah, A. | |
dc.contributor.author | Pavel-Dinu, M. | |
dc.contributor.author | Hendel, A. | |
dc.contributor.author | Porteus, M. | |
dc.contributor.author | Roncarolo, M. G. | |
dc.contributor.author | Bacchetta, R. | |
dc.contributor.funder | National Institute of Allergy and Infectious Diseases | en |
dc.contributor.funder | California Institute for Regenerative Medicine | en |
dc.contributor.funder | Stanford University | en |
dc.contributor.funder | Sutardja Foundation, United States | en |
dc.contributor.funder | Cancer Prevention and Research Institute of Texas | en |
dc.contributor.funder | Agency for Science, Technology and Research | en |
dc.date.accessioned | 2021-01-15T13:00:16Z | |
dc.date.available | 2021-01-15T13:00:16Z | |
dc.date.issued | 2020-05-06 | |
dc.date.updated | 2021-01-15T12:32:02Z | |
dc.description.abstract | 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. | en |
dc.description.sponsorship | National Institute of Allergy and Infectious Diseases (R21 AI123896); California Institute for Regenerative Medicine (DISC2-09526); Stanford University (1110504-308-DHBTC; Stanford NIH-NCATS-CTSA, UL1 TR001085; 1182084-100-DHDEZ; Masters of Science in Medicine scholarship); Sutardja Foundation, United States (1198779-101-GHFBB); Cancer Prevention and Research Institute of Texas (RR140081 and RR170721) | en |
dc.description.status | Peer reviewed | en |
dc.description.version | Published Version | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.articleid | eaaz0571 | en |
dc.identifier.citation | Goodwin, M., Lee, E., Lakshmanan, U., Shipp, S., Froessl, L., Barzaghi, F., Passerini, L., Narula, M., Sheikali, A., Lee, C. M., Bao, G., Bauer, C. S., Miller, H. K., Garcia-Lloret, M., Butte, M. J., Bertaina, A., Shah, A., Pavel-Dinu, M., Hendel, A., Porteus, M., Roncarolo, M. G. and Bacchetta, R. (2020) 'CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells', Science Advances, 6(19), eaaz0571 (17pp). doi: 10.1126/sciadv.aaz0571 | en |
dc.identifier.doi | 10.1126/sciadv.aaz0571 | en |
dc.identifier.endpage | 17 | en |
dc.identifier.issn | 2375-2548 | |
dc.identifier.issued | 19 | en |
dc.identifier.journaltitle | Science Advances | en |
dc.identifier.startpage | 1 | en |
dc.identifier.uri | https://hdl.handle.net/10468/10924 | |
dc.identifier.volume | 6 | en |
dc.language.iso | en | en |
dc.publisher | American Association for the Advancement of Science | en |
dc.rights | © 2020, The Authors. Some rights reserved. Exclusive licensee: American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | en |
dc.subject | IPEX syndrome | en |
dc.subject | Forkhead box protein 3 gene | en |
dc.subject | FOXP3 | en |
dc.subject | Immune regulation | en |
dc.subject | Gene correction | en |
dc.title | CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells | en |
dc.type | Article (peer-reviewed) | en |
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