AAV vectors encoding a hyper-functional factor IX (FIX-Padua, R338L) has been explored for the treatment of hemophilia B. In dogs and mouse models of disease the use of such variant resulted in beneficial therapeutic effect and, at same time, allowed reducing the AAV vector dosage and, therefore, the risk of cellular immune response to vector capsid, which is one of the main complications of AAV GT for hemophilia B (18, 47, 48). This evidence concerns the gene F9 and hemophilia B.