{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:09:13Z","timestamp":1790766553409,"version":"4.1.0"},"reference-count":101,"publisher":"Rockefeller University Press","issue":"2","license":[{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":236,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007805","name":"Coll\u00e8ge de France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,1,6]]},"abstract":"<jats:p>Ex vivo retrovirally mediated gene therapy has been shown within the last 20 yr to correct the T cell immunodeficiency caused by \u03b3c-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 (&amp;lt;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\u2013Aldrich syndrome, while further applications are pending. Genome editing of the mutated gene may be envisaged as an alternative strategy to treat SCID diseases.<\/jats:p>","DOI":"10.1084\/jem.20190607","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T15:59:26Z","timestamp":1576166366000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":94,"title":["Gene therapy for severe combined immunodeficiencies and beyond"],"prefix":"10.1084","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4025-5983","authenticated-orcid":true,"given":"Alain","family":"Fischer","sequence":"first","affiliation":[{"name":"Imagine Institute, Paris, France 1"},{"name":"Immunology and Pediatric Hematology Department, Assistance Publique-H\u00f4pitaux de Paris, Paris, France 2"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR 1163, Paris, France 3"},{"name":"Coll\u00e8ge de France, Paris, France 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salima","family":"Hacein-Bey-Abina","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Technologies Chimiques et Biologiques pour la Sant\u00e9, UMR8258 Centre National de la Recherche Scientifique - U1267 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Facult\u00e9 de Pharmacie de Paris, Universit\u00e9 Paris Descartes, Paris, France 5"},{"name":"Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud, H\u00f4pital Kremlin-Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris, Le Kremlin Bic\u00eatre, France 6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"key":"2023072610002932200_bib1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233151","article-title":"Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome","volume":"341","author":"Aiuti","year":"2013","journal-title":"Science."},{"key":"2023072610002932200_bib2","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1056\/NEJMoa0805817","article-title":"Gene therapy for immunodeficiency due to adenosine deaminase deficiency","volume":"360","author":"Aiuti","year":"2009","journal-title":"N. 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