{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:41:56Z","timestamp":1790912516856,"version":"4.1.0"},"reference-count":31,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,20]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Sickle cell disease (SCD) is characterized by chronic hemolysis, and painful vaso-occlusive episodes (VOE). High levels of fetal hemoglobin (HbF) attenuate the disease phenotype. We used a lentivirus vector (LVV) expressing a short hairpin RNA embedded in a microRNA (shmiR) that targets BCL11A in erythrocytes to induce HbF in a first-in-human study in SCD. The purpose of the study was to assess hematopoietic stem\/progenitor cells collection, transduction parameters, safety, HbF induction, and durability. Eleven eligible patients with SCD underwent hematopoietic stem cell (HSC) collection. Plerixafor-mobilized peripheral blood HSCs required for manufacturing were obtained in 1 mobilization cycle for 10 of 11 participants, and 11 of 11 patient products were successfully manufactured with a median time to release of product of 39 days. Ten patients were infused with HSCs transduced with the shmiR vector. Engraftment occurred in all 10 patients. At a median follow-up of 58 months (range, 35-82) after infusion, there were no adverse events attributed to the vector. The transduction efficiency was 93.1%. One patient demonstrated low engraftment of the transduced cells and had suboptimal HbF induction. In the remaining 9 patients, at 2 years after treatment, the peripheral blood demonstrated 71% F cells with 11.9 pg HbF per F cells, and both parameters remained stable in 9 patients with \u226548 months follow-up. All patients who had VOEs before gene therapy demonstrated sustained mitigation of pain events. These data demonstrate excellent manufacturing efficiency, efficacy and safety of targeting BCL11A using a shmiR LVV, and long-term durability of the shmiR vector, leading to a pivotal, multisite, phase 2 trial that is currently underway (NCT05353647). This trial was registered at www.clinicaltrials.gov as NCT03282656.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2026033871","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:10:42Z","timestamp":1780485042000},"page":"957-966","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["Long-term stability of posttranscriptional genetic silencing of BCL11A using a shmiR vector in sickle cell disease"],"prefix":"10.1182","volume":"148","author":[{"given":"Erica B.","family":"Esrick","sequence":"first","affiliation":[{"name":"1Division of Hematology\/Oncology, Boston Children's Hospital, Boston, MA"},{"name":"2Division of Pediatric Hematology\/Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"3Department of Pediatrics, Harvard Medical School, Boston, 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Ellen","family":"Grant","sequence":"additional","affiliation":[{"name":"3Department of Pediatrics, Harvard Medical School, Boston, MA"},{"name":"9Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA"},{"name":"10Department of Radiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic D.","family":"Bushman","sequence":"additional","affiliation":[{"name":"8Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1840-6087","authenticated-orcid":false,"given":"Donald B.","family":"Kohn","sequence":"additional","affiliation":[{"name":"7Division of Pediatric Hematology\/Oncology, Department of Pediatrics, University of California Los Angelas David Geffen School of Medicine, Los Angeles, 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