Coagulation Factor IX (FIX) (Padua variant) (FIX-Padua)

Coagulation Factor IX (Padua variant) is a hyperfunctional form of the human Factor IX protein, characterized by a leucine substitution for arginine at position 338 (R338L) (Simioni et al., 2009, NEJM). This specific variant exhibits approximately 8-fold higher procoagulant activity compared to wild-type Factor IX, making it a preferred transgene for Hemophilia B gene therapy (Monahan et al., 2015, Blood). In these therapies, the transgene is delivered to the nuclei of hepatocytes using viral vectors, typically adeno-associated virus (AAV), where it serves as a template for the endogenous production of the clotting factor (Pipe et al., 2023, NEJM). By establishing long-term expression of FIX-Padua in the liver, the treatment aims to convert a severe bleeding phenotype into a mild or asymptomatic one. Clinical applications include FDA-approved therapies like etranacogene dezaparvovec (Hemgenix) and fidanacogene elaparvovec (Beqvez), which have demonstrated the ability to significantly reduce annual bleeding rates (FDA, 2022; FDA, 2024). The use of the Padua variant allows for lower vector doses while achieving therapeutic levels of clotting activity, though it requires careful monitoring for potential thrombotic risks and hepatotoxicity (Croteau et al., 2023, Lancet Haematology).

Other names

Factor IX PaduaFIX-R338LF9 PaduaChristmas factor PaduaCoagulation Factor IX

Gene replacement therapy via AAV-mediated delivery of a hyperfunctional Factor IX transgene to hepatocytes.