{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:25:40Z","timestamp":1791419140401,"version":"4.3.3"},"reference-count":111,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BioMarin"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Historically, the standard of care for hemophilia A has been intravenous administration of exogenous factor VIII (FVIII), either as prophylaxis or episodically. The development of emicizumab, a humanized bispecific monoclonal antibody mimicking activated FVIII, was a subsequent advance in treatment. However, both exogenous FVIII and emicizumab require repeated and lifelong administration, negatively impacting patient quality of life. A recent breakthrough has been the development of gene therapy. This allows a single intravenous treatment that could result in long-term expression of FVIII, maintenance of steady-state plasma concentrations, and minimization (or possibly elimination) of bleeding episodes for the recipient\u2019s lifetime. Several gene therapies have been assessed in clinical trials, with positive outcomes. Valoctocogene roxaparvovec (an adeno-associated viral 5-based therapy encoding human B domain-deleted FVIII) is expected to be the first approved gene therapy in European countries, including Italy, in 2022. Some novel challenges exist including refining patient selection criteria, managing patient expectations, further elucidation of the durability and variability of transgene expression and long-term safety, and the development of standardized \u2018hub and spoke\u2019 centers to optimize and monitor this innovative treatment. Gene therapy represents a paradigm shift, and may become a new reference standard for treating patients with hemophilia A.<\/jats:p>","DOI":"10.3390\/ijms231810228","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T20:52:51Z","timestamp":1662497571000},"page":"10228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Arrival of Gene Therapy for Patients with Hemophilia A"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-1317","authenticated-orcid":false,"given":"Giancarlo","family":"Castaman","sequence":"first","affiliation":[{"name":"Center for Bleeding Disorders, Department of Oncology, Careggi University Hospital, Largo Brambilla 3, 50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Di Minno","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Hemo-Coagulation Diseases, Federico II University, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-8849","authenticated-orcid":false,"given":"Raimondo","family":"De Cristofaro","sequence":"additional","affiliation":[{"name":"Servizio Malattie Emorragiche e Trombotiche, Dipartimento di Medicina e Chirurgia Traslazionale, Fondazione Policlinico Universitraio \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica S. Cuore Roma, Largo Francesco Vito, 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-9864","authenticated-orcid":false,"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione Luigi Villa, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, Via Pace 9, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1055\/s-0041-1722862","article-title":"Gene Therapy for Inherited Bleeding Disorders","volume":"47","author":"Arruda","year":"2021","journal-title":"Semin. Thromb. 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