Recent Advances in Gene Therapy for Hemophilia.

Hemophilia, an X-linked monogenic disorder, arises from mutations in the or genes, which encode clotting factor VIII (FVIII) or clotting factor IX (FIX), respectively. 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' 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' 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.