{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:10:42Z","timestamp":1780571442981,"version":"3.54.1"},"reference-count":49,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:p>\n                    Severe combined immunodeficiency (SCID) encompasses rare primary immunodeficiency disorders characterized by deficient T-cell development, which leads to a severely compromised immune system and susceptibility to life-threatening infections. Among SCID subtypes, IL7RA-SCID is caused by mutations in the interleukin 7 receptor alpha chain (IL7RA) and represents a significant subset of patients with limited treatment options. This study investigated the efficacy of a self-inactivating (SIN) alpharetroviral vector (ARV) engineered to deliver a codon-optimized\n                    <jats:italic toggle=\"yes\">IL7RA<\/jats:italic>\n                    cDNA to restore T-cell development in\n                    <jats:italic toggle=\"yes\">Il7r<\/jats:italic>\n                    -knockout mice. We compared the elongation factor 1 alpha short (EFS) promoter and the lymphoid-restricted Lck promoter for their ability to drive IL7RA expression and found that the EFS promoter enabled robust and sustained IL7RA expression that led to the functional rescue of T-lymphopoiesis\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . Conversely, though effective\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    , the Lck promoter failed to produce viable T-cell populations\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . Our results highlight the potential of using SIN-ARVs as a gene therapy (GT) strategy for treating IL7RA-SCID. Importantly, sustained production of T-lymphocytes was found in both primary and secondary transplant recipient animals with no adverse effects, supporting the safety and feasibility of this approach. Overall, this study provides valuable insights into the development of GT for IL7RA-SCID and underscores the clinical potential of an EFS-driven SIN-ARV to restore IL7RA-deficient immune function.\n                  <\/jats:p>","DOI":"10.1089\/hum.2024.103","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T07:27:45Z","timestamp":1723793265000},"page":"669-679","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Alpharetroviral Vector\u2013Mediated Gene Therapy for IL7RA-Deficient Severe Combined Immunodeficiency"],"prefix":"10.1177","volume":"35","author":[{"given":"Teng-Cheong","family":"Ha","sequence":"first","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany"},{"name":"REBIRTH, Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany"},{"name":"REBIRTH, Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6097-6115","authenticated-orcid":false,"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[{"name":"Infection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Center, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2743-0070","authenticated-orcid":false,"given":"Axel","family":"Schambach","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany"},{"name":"REBIRTH, Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany"},{"name":"Division of Hematology\/Oncology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, 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Gene Therapy Clinical Trial Halted as Cancer Risk Surfaces | Science. AAAS; n.d. 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