{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:41:09Z","timestamp":1792474869427,"version":"4.5.0"},"reference-count":104,"publisher":"SAGE Publications","issue":"11-12","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"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":["Stem Cells and Development"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:p>Hematopoietic stem cells (HSCs) are multipotent stem cells capable of differentiating into all types of blood and immune progeny and endowed with self-renewal capacity to enable lifelong hematopoiesis. Based on these unique characteristics, HSCs are utilized as a cell source for cell and gene therapies. During its dawning period, HSC-based therapies faced significant challenges due to inefficient gene transfer and insertional leukemogenesis. However, technological advances, such as the use of HIV-derived lentiviral vectors and cellular promoters, have established HSC gene therapy as a powerful treatment modality for patients with congenital monogenic diseases, leading to approved therapies commercially available in Europe and the United States. HSC-based therapies are now being explored for broader indications, including cancer, autoimmune, and infectious diseases. Innovative concepts achievable with HSCs\u2014such as delivering therapeutic proteins to hard-to-reach tissues, in\u00a0vivo delivery of antibodies and immune cells, and molecular shielding\u2014have been proposed, offering new therapeutic approaches. Moreover, technological innovations in related fields, including more precise gene expression control and reduced-toxicity bone marrow conditioning, are expanding the range of applications. HSC-based cell and gene therapies are therefore evolving into a therapeutic modality applicable beyond monogenic diseases to a broader range of indications, to provide therapeutic value to patients with intractable diseases.<\/jats:p>","DOI":"10.1177\/15473287261444631","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:29:47Z","timestamp":1777958987000},"page":"201-211","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hematopoietic Stem Cell-Based Cell and Gene Therapy Beyond Monogenic Diseases"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-9005","authenticated-orcid":false,"given":"Masayuki","family":"Kai","sequence":"first","affiliation":[{"name":"Research Strategy Department, Research Division, Kyowa Kirin Co., Ltd., Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"Mavilio","sequence":"additional","affiliation":[{"name":"Orchard Therapeutics, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-570200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809958"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/14.4.955"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2307\/3570892"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.51.1.29"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2898810"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017934"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.01.006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26178381"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejm197504172921605"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejm197504242921706"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2147\/sccaa.s6815"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.245688"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2017.05.003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.185.4148.303"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.175.4025.949"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2022.05.001"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/310476a0"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0798-775"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5235.470"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5466.669"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070104"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1003548"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci35798"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci35700"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0020-9"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007280"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.10.001"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.72.10.8150-8157.1998"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26178497"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2985"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v110.11.3732.3732"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-283523"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14226"},{"key":"e_1_3_3_36_2","unstructured":"U.S. Food and Drug Administration. Approved Cellular and Gene Therapy Products. Available from: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/approved-cellular-and-gene-therapy-products"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1700554"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2117175"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2113206"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2309676"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2405727"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-3026(19)30021-3"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.04.029"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03484-5"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84938-8"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izac205"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izae020.087"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.11.140"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2106596"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2021.39.15_suppl.2532"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.18609\/cgti.2020.157"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-178212"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-177139"},{"key":"e_1_3_3_54_2","unstructured":"Luna S Feist W Utz A et al. Engineered hematopoietic stem cells give rise to therapeutic antibody secreting b cells. In: 28th Annual Meeting American Society of Gene & Cell Therapy; 2025."},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1819992116"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0277-8"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06496-5"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2023.101135"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.013"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-165289"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-190037"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.12.311"},{"key":"e_1_3_3_63_2","unstructured":"Vor Bio Announces Exploration of Strategic Alternatives to Maximize Shareholder Value. 2025. Available from: https:\/\/ir.vorbio.com\/news-releases\/news-release-details\/vor-bio-announces-exploration-strategic-alternatives-maximize\/ [Last accessed: November29 2025]."},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202249109"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.2.1308"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/73208"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-120535"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403823"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi1145"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07456-3"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.102"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.02.026"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.141502"},{"key":"e_1_3_3_74_2","unstructured":"Louvet C Chen Y Rosenberg E et al. In Vivo Self-Renewing HSC-Based CAR-NK Cell Factory. In: 28th Annual Meeting American Society of Gene & Cell Therapy; 2025."},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811984116"},{"key":"e_1_3_3_76_2","unstructured":"Crawford G. HSC-Derived CAR-Treg Gene Therapy: A Novel Approach for the Treatment of Multiple Sclerosis. In: The European Society of Gene and Cell Therapy (ESGCT) 31st Annual Congress. 2024."},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.04.004"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v96.10.3392.h8003392_3392_3398"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2022.11.005"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.464"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-208014"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00095"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5319.1719"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1106152"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2727-2_6"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.03.001"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-514778"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2024.09.001"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08201-x"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024636"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.101"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03817-1"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.20-0247"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27689"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2022.10.003"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03612-0"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03576-1"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2021.102270"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.07.014"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6967"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018252"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007975"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.12.003"},{"key":"e_1_3_3_104_2","unstructured":"Ensoma pipeline. Available from: https:\/\/ensoma.com\/pipeline\/ [Last accessed: November29 2025]."},{"key":"e_1_3_3_105_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.03.016"}],"container-title":["Stem Cells and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15473287261444631","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15473287261444631","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15473287261444631","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:29:13Z","timestamp":1792474153000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15473287261444631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":104,"journal-issue":{"issue":"11-12","published-print":{"date-parts":[[2026,6,1]]}},"alternative-id":["10.1177\/15473287261444631"],"URL":"https:\/\/doi.org\/10.1177\/15473287261444631","relation":{},"ISSN":["1547-3287","1557-8534"],"issn-type":[{"value":"1547-3287","type":"print"},{"value":"1557-8534","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]}}}