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Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells

التفاصيل البيبلوغرافية
العنوان: Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells
المؤلفون: Pierre Charneau, Julia Hauer, Julie Rivière, Marc Le Lorc'h, Jean-Pierre de Villartay, Pauline Soulas-Sprauel, Anne Galy, Michèle Malassis-Séris, Johanna Blondeau, Alexandrine Garrigue, Alain Fischer, Frederique Pâques, Nicole Brousse, Marina Cavazzana-Calvo, Serge Romana, Fatine Benjelloun, Daniel Stockholm, Annick Lim, Corinne Demerens-de Chappedelaine
المساهمون: Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Généthon, Développement des Lymphocytes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Histologie-Embryologie et Cytogénétique Assistance Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et Cytologie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Cellectis SA, CELLECTIS, Virologie moléculaire et Vectorologie, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Unité d'Immunologie et Hématologie Pédiatrique, Service d'Hématologie, Département de Biothérapie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), This work was funded by grants from Institut National de la Santé et de la Recherche (INSERM), the Association Française contre les Myopathies (AFM) contract GAT0203, the Consortium National de Recherche en Génomique, the EC contract QLK3-CT-1999-00859, the Consert contract no. 005242, the Inherinet contract QLK3-CT-2001-00427, the Agence Nationale de la Recherche grant 05-MRAR-004, and a grant from Amgen-France (M. de Garidel and C. Cailliot). F.B.'s fellowship was provided by the AFM. P.S.S. was supported by INSERM, Electricité de France, and the Fondation Singer Polignac. J.H. is a fellow of the Deutsche Akademie der Naturforscher Leopoldina (BMBF-LPD 9901/8-149), Immunologie moléculaire et biothérapies innovantes (IMBI), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Genethon, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
المصدر: Molecular Therapy
Molecular Therapy, Cell Press, 2008, 16 (8), pp.1490-9. ⟨10.1038/mt.2008.118⟩
Molecular Therapy, 2008, 16 (8), pp.1490-1499. ⟨10.1038/mt.2008.118⟩
Molecular Therapy, Nature Publishing Group, 2008, 16 (8), pp.1490-9. 〈10.1038/mt.2008.118〉
Molecular Therapy, 2008, 16 (8), pp.1490-9. ⟨10.1038/mt.2008.118⟩
Molecular Therapy, Nature Publishing Group, 2008, 16 (8), pp.1490-9. ⟨10.1038/mt.2008.118⟩
سنة النشر: 2008
مصطلحات موضوعية: Male, CD3 Complex, MESH: Antigens, CD3, Genetic enhancement, T-Lymphocytes, MESH: Interleukin-2 Receptor alpha Subunit, MESH: Antigens, CD4, MESH: Flow Cytometry, MESH: Mice, Knockout, MESH: Hematopoietic Stem Cells, Mice, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Genetic Vectors, Transduction, Genetic, Chromosome instability, MESH : Antigens, CD44, Drug Discovery, MESH : Female, MESH: Animals, Cells, Cultured, MESH: Lentivirus, Mice, Knockout, 0303 health sciences, B-Lymphocytes, Hematopoietic Stem Cell Transplantation, Nuclear Proteins, MESH : Interleukin-2 Receptor alpha Subunit, MESH: Transduction, Genetic, Flow Cytometry, MESH : Genetic Vectors, 3. Good health, Haematopoiesis, MESH : Lentivirus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Hyaluronan Receptors, 030220 oncology & carcinogenesis, Knockout mouse, CD4 Antigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Female, Stem cell, MESH : Gene Therapy, MESH: Cells, Cultured, MESH : Flow Cytometry, MESH : Male, CD8 Antigens, Genetic Vectors, MESH : Severe Combined Immunodeficiency, MESH: Severe Combined Immunodeficiency, MESH : Transduction, Genetic, Thymus Gland, Biology, MESH: Antigens, CD44, MESH : B-Lymphocytes, Viral vector, 03 medical and health sciences, MESH : Hematopoietic Stem Cell Transplantation, MESH: B-Lymphocytes, MESH : Mice, MESH : Cells, Cultured, Genetics, medicine, Animals, MESH : Thymus Gland, Molecular Biology, MESH: Mice, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, MESH : T-Lymphocytes, Pharmacology, Severe combined immunodeficiency, MESH : Hematopoietic Stem Cells, Lentivirus, Interleukin-2 Receptor alpha Subunit, MESH : Nuclear Proteins, MESH: Thymus Gland, Genetic Therapy, medicine.disease, Endonucleases, Hematopoietic Stem Cells, MESH: Male, Transplantation, MESH: T-Lymphocytes, Immunology, Cancer research, MESH : Mice, Knockout, MESH : Antigens, CD4, Severe Combined Immunodeficiency, MESH : Animals, MESH : Antigens, CD3, MESH: Antigens, CD8, MESH: Gene Therapy, MESH : Antigens, CD8, MESH: Nuclear Proteins, MESH: Female
الوصف: International audience; Patients with mutations in the Artemis gene display a complete absence of T- and B lymphocytes, together with increased cellular radiosensitivity; this leads to a radiosensitive severe combined immunodeficiency (RS-SCID). Allogenic hematopoietic stem-cell (HSC) transplantation is only partially successful in the absence of an human leukocyte antigen-genoidentical donor, and this has prompted a search for alternative therapeutic approaches such as gene therapy. In this study, a self-inactivated lentiviral vector expressing Artemis was used to complement the Artemis knockout mouse (Art(-/-)). Transplantation of Artemis-transduced HSCs into irradiated Art(-/-) mice restored a stable (over a 15-month period of follow-up) and functional T- and cell repertoire that was comparable to that of control mice. The success of secondary transplantations demonstrated that the HSCs had been transduced. One of thirteen mice developed a thymoma 6 months after gene therapy. Although thymic cells were seen to be carrying two lentiviral integration sites, there was no evidence of lentivirus-driven oncogene activation. The Art(-/-) mice were found to be prone to develop T-cell lymphomas, either spontaneously or after irradiation. These data indicate that the observed lymphoproliferation was probably the consequence of the chromosomal instability associated with the Artemis-deficient background. As a whole, our work provides a basis for supporting the gene therapy approach in Artemis-deficient SCID.
تدمد: 1525-0024
1525-0016
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd124b09ba43175b099dad8fc5b27673
https://pubmed.ncbi.nlm.nih.gov/18560421
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....dd124b09ba43175b099dad8fc5b27673
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15250024
15250016