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Current treatment primarily relies on replacement therapy, involving frequent and costly infusions of FVIII or FIX concentrates. While effective, these treatments come with the risk of developing neutralizing antibodies (inhibitors) against the infused factor. In recent years, non\u2010factor replacement therapies have emerged as innovative treatment options, offering enhanced efficacy especially for patients with inhibitors. Despite their advantages, these approaches still fall short of providing a definitive, long\u2010term cure. Since hemophilia is a monogenic disease, it presents an excellent opportunity for cell and gene therapy approaches aimed at achieving durable treatment and potentially a cure. Over the past three decades, remarkable advancements have been made in hemophilia gene therapy, culminating in the approval of Valoctocogene roxaparvovec (ROCTAVIAN, AAV\u2010FVIII) and Etranacogene dezaparvovec (HEMGENIX, AAV\u2010FIX) for patients with severe HA and HB, respectively. Nevertheless, gene therapy poses questions regarding its long\u2010term efficacy and safety. This review synthesizes findings from clinical trials, addresses persistent challenges in hemophilia gene therapy, and underscores the biological constraints and limitations inherent to viral vector\u2010based approaches.<\/jats:p>","DOI":"10.1002\/iub.70087","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:45:14Z","timestamp":1768815914000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Balancing Promise and Peril: Hemophilia Gene Therapy Insights"],"prefix":"10.1002","volume":"78","author":[{"given":"Saicharan","family":"Akula","sequence":"first","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi del Piemonte Orientale  Novara 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