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As a prominent hereditary coagulation disorder, hemophilia is clinically manifested by spontaneous hemorrhagic episodes. Severe cases may progress to complications such as stroke and arthropathy, significantly compromising patients\u2019 quality of life. Hemophilia has a monogenic nature, coupled with quantifiable therapeutic endpoints and predictable treatment outcomes. These characteristics render it an ideal candidate for gene therapy studies. Currently, Food and Drug Administration (FDA)-approved gene therapies utilize recombinant adeno-associated virus (AAV) vectors to deliver functional transgene cassettes to hepatocytes. These therapies offer distinct advantages: a single intravenous administration achieves sustained FVIII and FIX activity levels, providing robust hemostatic control while markedly enhancing patients\u2019 quality of life. However, several challenges remain, including immunogenicity, thrombotic risks, potential gene integration, and prohibitive costs. Future endeavors should prioritize expanding patient eligibility and integrating precision gene-editing technologies to mitigate these limitations. In this review, we provide a comprehensive overview of recent advances and emerging strategies in hemophilia gene therapy, with a particular focus on clinical translation and technological innovation. Ongoing research in this field remains pivotal to overcome existing barriers, enhance treatment accessibility, and ultimately realize curative potential for patients with hemophilia.\n                  <\/jats:p>","DOI":"10.1177\/10760296251378455","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T15:28:13Z","timestamp":1757518093000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Recent Advances in Gene Therapy for Hemophilia"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1479-7631","authenticated-orcid":false,"given":"Xiaojuan","family":"Pang","sequence":"first","affiliation":[{"name":"Applied Research Center for Genetic Resources of Bioactive Substances, Guangdong Xin\u2019an Polytechnic, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxian","family":"Fu","sequence":"additional","affiliation":[{"name":"Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Laboratory, Division of Hematology\/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Tang","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Laboratory, Division of Hematology\/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cia-Hin","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfei","family":"Wen","sequence":"additional","affiliation":[{"name":"Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Syno Minicircle Biotechnology Co., Ltd., Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongman","family":"Xue","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Laboratory, Division of Hematology\/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00278-x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/hae.15109"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-07-820720"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2502741"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-024-03824-y"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1160\/th10-11-0725"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1688445"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-742312"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01845-0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-024-02017-4"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01788-y"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003777"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2019000007"},{"issue":"3","key":"e_1_3_3_16_2","article-title":"Acquired hemophilia A: An update on the etiopathogenesis, diagnosis, and treatment","volume":"13","author":"Zanon E","year":"2023","unstructured":"Zanon E. 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