In this issue of Blood, Finn et al have taken a factor IX variant with increased specific activity associated with thrombophilia and used it to improve gene therapy of hemophilia B in dogs, and Cantore et al have shown similar results in mice.
Here we generated codon-usage optimized and hyperfunctional factor IX (FIX) transgenes carrying an R338L amino acid substitution (FIX Padua), previously associated with clotting hyperactivity and thrombophilia.