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However, a major limitation is the lack of a highly efficient and safe genetic manipulation system for transplantable primary human hepatocytes (PHHs). Here, we reported that proliferating human hepatocytes (ProliHHs) cultured in vitro showed high susceptibility to lentivirus\u2010mediated genetic modification and maintained cellular phenotypes after lentiviral infection. Human factor VIII expression was introduced through F8\u2010Lentivirus\u2010mediated transduction of ProliHHs followed by xenotransplantation into immunocompromised haemophilia A mice. We demonstrated that these F8\u2010modified ProliHHs could effectively repopulate the mouse liver, resulting in therapeutic benefits in mouse models. Furthermore, no genotoxicity was detected in F8\u2010modified ProliHHs using lentiviral integration site analysis. Thus, this study demonstrated, for the first time, the feasibility and safety of lentiviral modification in ProliHHs to induce the expression of coagulation factor VIII in the treatment of haemophilia A.<\/jats:p>","DOI":"10.1111\/cpr.13467","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T05:42:06Z","timestamp":1684388526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ex vivo factor <scp>VIII<\/scp>\u2010modified proliferating human hepatocytes therapy for haemophilia A"],"prefix":"10.1111","volume":"56","author":[{"given":"Kun","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences University of Chinese Academy of Sciences  Shanghai 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