{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:25:29Z","timestamp":1790083529166,"version":"4.0.1"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"811","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,8,13]]},"abstract":"<jats:p>\n                    Sickle cell disease (SCD) is caused by a single nucleotide change in the \u03b2-globin gene that adenine base editors can convert to the nonpathogenic Makassar \u03b2-globin variant. Here, we evaluated the long-term efficiency and off-target editing potential of autologous Makassar base editing in three rhesus macaques as a step toward human translation. Base editing of CD34\n                    <jats:sup>+<\/jats:sup>\n                    CD90\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic stem cells (HSCs) at the Makassar locus reached greater than 60% efficiency using a bystander nucleotide as a proxy for the sickle cell target in cells from healthy macaques. No impact on myeloid and erythroid colony formation was seen, and clonal analysis revealed that &gt;90% of HSCs were edited, &gt;20% with biallelic editing. After transplantation of autologous gene-edited HSCs, all three macaques rapidly recovered neutrophils, red blood cells, and platelets with stable editing of 25.6%, on average, observed across nucleated blood cells. Similarly, the bone marrow stem cell compartment maintained over 20% of cells harboring mono- or biallelic edits. Off-target editing was assessed at over 900 candidate sites, with editing observed at eight sites, but no selection for or impact of these edits was observed throughout engraftment. These data support further translation of base editing of autologous HSCs for the treatment of patients with SCD.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adn2601","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T18:00:58Z","timestamp":1755108058000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Engraftment and persistence of\n                    <i>HBB<\/i>\n                    base-edited hematopoietic stem cells in nonhuman primates"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2842-4820","authenticated-orcid":true,"given":"Stefan","family":"Radtke","sequence":"first","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."},{"name":"Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7352-5260","authenticated-orcid":true,"given":"Emily","family":"Fields","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1808-7609","authenticated-orcid":true,"given":"Kyle","family":"Swing","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0494-7823","authenticated-orcid":true,"given":"Greta","family":"Kanestrom","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-9450","authenticated-orcid":true,"given":"Jonathan S.","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9343-0584","authenticated-orcid":true,"given":"Dnyanada","family":"Pande","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Enstrom","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA 98109, 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02142, USA."},{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."},{"name":"Howard Hughes Medical Institute, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7869-2615","authenticated-orcid":true,"given":"Gregory A.","family":"Newby","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA."},{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."},{"name":"Howard Hughes Medical Institute, Cambridge, MA 02142, USA."},{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, 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