دورية أكاديمية
Precise CRISPR-Cas9 gene repair in autologous memory T cells to treat familial hemophagocytic lymphohistiocytosis.
| العنوان: | Precise CRISPR-Cas9 gene repair in autologous memory T cells to treat familial hemophagocytic lymphohistiocytosis. |
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| المؤلفون: | Li X; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., Wirtz T; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., Weber T; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., Lebedin M; Immune Mechanisms and Human Antibodies, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), 10117 Berlin, Germany., Lowenstein ED; Developmental Biology/Signal Transduction, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., Sommermann T; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., Zach A; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), 10117 Berlin, Germany., Yasuda T; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., de la Rosa K; Immune Mechanisms and Human Antibodies, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.; Center of Biological Design, Berlin Institute of Health (BIH) at Charité, 13125 Berlin, Germany., Chu VT; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.; Genome Engineering & Disease Models, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., Schulte JH; Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), 10117 Berlin, Germany., Müller I; Division of Pediatric Stem Cell Transplantation and Immunology, Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Kocks C; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.; Developmental Biology/Signal Transduction, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany., Rajewsky K; Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany. |
| المصدر: | Science immunology [Sci Immunol] 2024 Feb 02; Vol. 9 (92), pp. eadi0042. Date of Electronic Publication: 2024 Feb 02. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]- |
| مواضيع طبية MeSH: | Lymphohistiocytosis, Hemophagocytic*/genetics , Lymphohistiocytosis, Hemophagocytic*/therapy , Epstein-Barr Virus Infections*/genetics , Epstein-Barr Virus Infections*/therapy, Animals ; Mice ; Humans ; CRISPR-Cas Systems ; Memory T Cells ; Herpesvirus 4, Human ; Membrane Proteins/genetics |
| مستخلص: | Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, often fatal immune deficiency characterized by severe systemic hyperinflammation. Although allogeneic bone marrow transplantation can be curative, more effective therapies are urgently needed. FHL is caused by inactivating mutations in proteins that regulate cellular immunity. Here, we used an adeno-associated virus-based CRISPR-Cas9 system with an inhibitor of nonhomologous end joining to repair such mutations in potentially long-lived T cells ex vivo. Repaired CD8 memory T cells efficiently cured lethal hyperinflammation in a mouse model of Epstein-Barr virus-triggered FHL2, a subtype caused by perforin-1 ( Prf1 ) deficiency. Furthermore, repair of PRF1 and Munc13-4 ( UNC13D )-whose deficiency causes the FHL subtype FHL3-in mutant memory T cells from two critically ill patients with FHL restored T cell cytotoxicity. These results provide a starting point for the treatment of genetic T cell immune dysregulation syndromes with repaired autologous T cells. |
| المشرفين على المادة: | 0 (UNC13D protein, human) 0 (Membrane Proteins) |
| تواريخ الأحداث: | Date Created: 20240202 Date Completed: 20240205 Latest Revision: 20240205 |
| رمز التحديث: | 20240205 |
| DOI: | 10.1126/sciimmunol.adi0042 |
| PMID: | 38306418 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2470-9468 |
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| DOI: | 10.1126/sciimmunol.adi0042 |