{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:16:37Z","timestamp":1787926597156,"version":"build-2784847793"},"reference-count":95,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institute of Health","award":["R01DK099317"],"award-info":[{"award-number":["R01DK099317"]}]},{"name":"Breakthrough T1D","award":["3-SRA-2024-1463-S-B"],"award-info":[{"award-number":["3-SRA-2024-1463-S-B"]}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["GNT1162066"],"award-info":[{"award-number":["GNT1162066"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"abstract":"<jats:p>\n                    Gene therapy achieved through genetic manipulation and transfer of hematopoietic stem and progenitor cells (HSPC) is becoming an increasingly attractive option for personalized medicine. In the current clinical scenarios, use is restricted to overcoming genetic disorders, but it is envisioned that more diverse applications will be developed in the future. Immunotherapy of malignant disease already employs non-HSPC-based gene therapies, and there is a body of evidence that HSPC-mediated gene therapy has potential as a powerful immunotherapeutic for some diseases of immune dysregulation such as autoimmune disease and allergies. Administration of HSPC gene-engineered to encode antigen(s) induces antigen-specific immune tolerance in animal models. To translate this technology, we sought to identify whether human dendritic cells (DC) and other antigen-presenting cell populations derived from lentivirally transduced HSPC would express, process, and present antigens of interest. Lentiviral vectors were generated that encoded preproinsulin, a relevant autoantigen implicated in type 1 diabetes, or a control protein carrying a viral epitope along with reporter genes under transcriptional control of ubiquitous or antigen-presenting cell-directed promoters.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    , DC were differentiated from transduced HSPC and tested in antigen presentation assays using Jurkat lines carrying relevant type 1 diabetes-associated T cell receptors.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    , transduced HSPC were used to generate humanized mice, and the development of a range of antigen-presenting cells and their expression of lentivirus-encoded genes were determined. Antigen-presenting cell progeny of transduced HSPC expressed antigens and reporter genes both\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    -generated DC presented lentivirally encoded antigens. The studies characterize human chimerism and therapeutic gene expression in a new model and provide support for the use of HSPC-based gene therapies for immune dysregulation in humans.\n                  <\/jats:p>","DOI":"10.1177\/10430342261478743","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:15:05Z","timestamp":1787591705000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering Human Hematopoietic Stem and Progenitor Cells for Antigen Expression in Antigen-Presenting Cells"],"prefix":"10.1177","author":[{"given":"Clara","family":"Heider","sequence":"first","affiliation":[{"name":"Frazer Institute, The University of Queensland, Woolloongabba, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-8914","authenticated-orcid":false,"given":"Meg Louise","family":"Donovan","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Woolloongabba, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Walpole","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Woolloongabba, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Woolloongabba, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Alim","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Woolloongabba, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Buckle","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Woolloongabba, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Woolloongabba, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Barry","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences and Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart I.","family":"Mannering","sequence":"additional","affiliation":[{"name":"Immunology 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