{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:36:30Z","timestamp":1790735790715,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":329,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Canadian Blood Services Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gene editing blood-derived cells is an attractive approach to cure selected monogenic diseases but remains experimental. A systematic search of preclinical controlled studies is needed to determine the persistence of edited cells following reinfusion. All studies identified in our systematic search (to 20 October 2020) examining the use of CRISPR\/Cas9 gene editing in blood-derived cells for transplantation were included. Meta-analysis was performed to determine the engraftment and persistence of gene edited cells. A total of 3538 preclinical studies were identified with 15 published articles meeting eligibility for meta-analysis. These in vivo animal studies examined editing of hemoglobin to correct sickle cell disease (eight studies), inducing resistance to acquired immunodeficiency syndrome (two studies), and six other monogenic disorders (single studies). CRISPR-Cas9 edited hematopoietic stem and progenitor cells demonstrated equivalent early engraftment compared to controls in meta-analysis but persistence of gene-edited cells was reduced at later time points and in secondary transplant recipients. Subgroup analysis in studies targeting the hemoglobin gene revealed a significant reduction in the persistence of gene-edited cells whether homology-directed repair or nonhomologous end-joining were used. No adverse side effects were reported. Significant heterogeneity in study design and outcome reporting was observed and the potential for bias was identified in all studies. CRISPR-Cas9 gene edited cells engraft similarly to unedited hematopoietic cells. Persistence of gene edited cells, however, remains a challenge and improved methods of targeting hematopoietic stem cells are needed. Reducing heterogeneity and potential risk of bias will hasten the development of informative clinical trials.<\/jats:p>","DOI":"10.1002\/sctm.20-0520","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:47:05Z","timestamp":1614923225000},"page":"996-1007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Persistence of CRISPR\/Cas9 Gene Edited Hematopoietic Stem\u00a0Cells Following Transplantation: A Systematic Review and\u00a0Meta-Analysis of Preclinical Studies"],"prefix":"10.1093","volume":"10","author":[{"given":"Harinad B.","family":"Maganti","sequence":"first","affiliation":[{"name":"Canadian Blood Services, Stem Cells and Centre for Innovation, Ottawa, Ontario, Canada"},{"name":"Clinical Epidemiology & Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J. 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