Coagulation factor VIII (F8) gene (F8)

The Coagulation factor VIII (F8) gene encodes a critical protein cofactor essential for the intrinsic pathway of the blood coagulation cascade [2, 8]. Mutations in this gene result in Hemophilia A, an X-linked recessive disorder characterized by spontaneous bleeding and impaired hemostasis [1, 8]. In modern therapeutic contexts, the F8 gene is a primary target for gene therapy, where functional copies of the gene are delivered to the hepatocyte genome to restore endogenous protein production [1, 3]. Hepatocytes are the preferred target cells due to their high capacity for protein synthesis and their role in inducing immune tolerance to the transgene product [3, 5]. Current gene therapies, such as Valoctocogene roxaparvovec, utilize adeno-associated virus (AAV) vectors to deliver a B-domain deleted version of the F8 gene directly to the liver [10, 12]. Once the genetic material is established within the hepatocyte nuclei, the cells synthesize and secrete functional Factor VIII into the systemic circulation [1, 10]. This approach aims to provide a durable, potentially curative treatment that reduces or eliminates the need for regular prophylactic infusions of recombinant protein [2, 12]. However, challenges remain, including the potential for liver inflammation (transaminitis), immune responses against the viral vector, and a gradual decline in Factor VIII expression levels over time [9, 14].

Other names

Factor VIII geneF8CHEMAAntihemophilic factor geneF8B

Gene replacement therapy via AAV-mediated delivery of a functional F8 transgene to hepatocytes