{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:09:14Z","timestamp":1792001354156,"version":"4.4.0"},"reference-count":49,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Gene therapy offers the potential for a cure for patients with hemophilia by establishing continuous endogenous expression of factor VIII or factor IX (FIX) following transfer of a functional gene to replace the hemophilic patient\u2019s own defective gene. The hemophilias are ideally suited for gene therapy because a small increment in blood factor levels (\u22655% of normal) is associated with significant amelioration of bleeding phenotype in severely affected patients. In 2011, the St. Jude\/UCL phase 1\/2 trial was the first to provide clear evidence of a stable dose-dependent increase in FIX levels in patients with severe hemophilia B following a single administration of adeno-associated viral (AAV) vectors. Transgenic FIX expression has remained stable at \u223c5% of normal in the high-dose cohort over a 7-year follow-up period, resulting in a substantial reduction in spontaneous bleeding and FIX protein usage without toxicity. This study has been followed by unparalleled advances in gene therapy for hemophilia A and B, leading to clotting factor activity approaching normal or near-normal levels associated with a \u201czero bleed rates\u201d in previously severely affected patients following a single administration of AAV vectors. Thus, AAV gene therapies are likely to alter the treatment paradigm for hemophilia A and B. This review explores recent progress and the remaining limitations that need to be overcome for wider availability of this novel treatment of inherited bleeding disorders.<\/jats:p>","DOI":"10.1182\/hematology.2019000007","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T15:09:42Z","timestamp":1575644982000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":118,"title":["Gene therapy for hemophilia"],"prefix":"10.1182","volume":"2019","author":[{"given":"Amit C.","family":"Nathwani","sequence":"first","affiliation":[{"name":"Department of Haematology, UCL Cancer Institute, Katharine Dormandy Haemophilia and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, United Kingdom; and Freeline Therapeutics Ltd., Stevenage, United 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