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Gene therapy for severe combined immunodeficiencies and beyond.
J Exp Med. 2020 Jan 06; 217(2)JE

Abstract

Ex vivo retrovirally mediated gene therapy has been shown within the last 20 yr to correct the T cell immunodeficiency caused by γc-deficiency (SCID X1) and adenosine deaminase (ADA) deficiency. The rationale was brought up by the observation of the revertant of SCIDX1 and ADA deficiency as a kind of natural gene therapy. Nevertheless, the first attempts of gene therapy for SCID X1 were associated with insertional mutagenesis causing leukemia, because the viral enhancer induced transactivation of oncogenes. Removal of this element and use of a promoter instead led to safer but still efficacious gene therapy. It was observed that a fully diversified T cell repertoire could be generated by a limited set (<1,000) of progenitor cells. Further advances in gene transfer technology, including the use of lentiviral vectors, has led to success in the treatment of Wiskott-Aldrich syndrome, while further applications are pending. Genome editing of the mutated gene may be envisaged as an alternative strategy to treat SCID diseases.

Authors+Show Affiliations

Imagine Institute, Paris, France. Immunology and Pediatric Hematology Department, Assistance Publique-Hôpitaux de Paris, Paris, France. Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France. Collège de France, Paris, France.Unité de Technologies Chimiques et Biologiques pour la Santé, UMR8258 Centre National de la Recherche Scientifique - U1267 Institut National de la Santé et de la Recherche Médicale, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France. Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31826240

Citation

Fischer, Alain, and Salima Hacein-Bey-Abina. "Gene Therapy for Severe Combined Immunodeficiencies and Beyond." The Journal of Experimental Medicine, vol. 217, no. 2, 2020.
Fischer A, Hacein-Bey-Abina S. Gene therapy for severe combined immunodeficiencies and beyond. J Exp Med. 2020;217(2).
Fischer, A., & Hacein-Bey-Abina, S. (2020). Gene therapy for severe combined immunodeficiencies and beyond. The Journal of Experimental Medicine, 217(2). https://doi.org/10.1084/jem.20190607
Fischer A, Hacein-Bey-Abina S. Gene Therapy for Severe Combined Immunodeficiencies and Beyond. J Exp Med. 2020 Jan 6;217(2) PubMed PMID: 31826240.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene therapy for severe combined immunodeficiencies and beyond. AU - Fischer,Alain, AU - Hacein-Bey-Abina,Salima, PY - 2019/08/30/received PY - 2019/10/10/revised PY - 2019/11/06/accepted PY - 2019/12/12/entrez PY - 2019/12/12/pubmed PY - 2019/12/12/medline JF - The Journal of experimental medicine JO - J. Exp. Med. VL - 217 IS - 2 N2 - Ex vivo retrovirally mediated gene therapy has been shown within the last 20 yr to correct the T cell immunodeficiency caused by γc-deficiency (SCID X1) and adenosine deaminase (ADA) deficiency. The rationale was brought up by the observation of the revertant of SCIDX1 and ADA deficiency as a kind of natural gene therapy. Nevertheless, the first attempts of gene therapy for SCID X1 were associated with insertional mutagenesis causing leukemia, because the viral enhancer induced transactivation of oncogenes. Removal of this element and use of a promoter instead led to safer but still efficacious gene therapy. It was observed that a fully diversified T cell repertoire could be generated by a limited set (<1,000) of progenitor cells. Further advances in gene transfer technology, including the use of lentiviral vectors, has led to success in the treatment of Wiskott-Aldrich syndrome, while further applications are pending. Genome editing of the mutated gene may be envisaged as an alternative strategy to treat SCID diseases. SN - 1540-9538 UR - https://www.unboundmedicine.com/medline/citation/31826240/Gene_therapy_for_severe_combined_immunodeficiencies_and_beyond L2 - https://rupress.org/jem/article-lookup/doi/10.1084/jem.20190607 DB - PRIME DP - Unbound Medicine ER -
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