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At present, the only curative treatment for SCD is allogeneic or gene\u2010modified autologous hematopoietic stem cell (HSC) transplantation (Tx). HSC\u2010Tx carries considerable challenges\/risks to the patient largely due to the highly toxic conditioning required to achieve sufficient HSC engraftment. Furthermore, existing treatments often only commence in late childhood or adolescence, yet SCD's clinical manifestation start during infancy, placing the child at risk of potentially life\u2010threatening complications. Thus, there is an urgent unmet medical need for novel SCD therapies that can promise an early cure for this devastating disease following a single treatment. In utero transplantation (IUTx) could correct SCD prior to disease onset, allowing the birth of a healthy baby freed from the immense burden this malady exerts on the quality of life and socioeconomically. This review examines the physiological and immunological rationale, current evidence, and the feasibility and hurdles to the clinical translation of IUTx for SCD. We then highlight some of the exciting recent advances in nongenotoxic conditioning (NGC). We conclude the review by summarizing how these advances in NGC can promise to make HSC\u2010Tx (postnatal or in utero) widely available, affordable, safe, and effective for not only SCD but also a range of other monogenic disorders.<\/jats:p>","DOI":"10.1002\/pd.70142","type":"journal-article","created":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T16:49:08Z","timestamp":1775407748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Utero HSC Transplantation for Sickle Cell Disease: A Potential Therapeutic Approach That Overcomes Complications of Current Therapies"],"prefix":"10.1002","author":[{"given":"Oluwaseun O.","family":"Babatunde","sequence":"first","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine G.","family":"Bibby","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Atala","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u00e7a","family":"Almeida\u2010Porada","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-7556","authenticated-orcid":false,"given":"Christopher D.","family":"Porada","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.20"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.02.015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199612123352404"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00015"},{"key":"e_1_2_10_6_1","article-title":"In Utero Stem Cell Transplantation and Gene Therapy: Recent Progress and the Potential for Clinical Application","author":"McClain L. 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