Factor IX Padua for haemophilia B gene addition: universal adaptation and repeated success

Abstract

In The Lancet Haematology, Feng Xue and colleagues1 report 1 year of sustained mean factor IX (FIX) activity well into the mild range of haemophilia and sufficient to nearly eliminate bleeding events among ten Chinese participants with haemophilia B who received BBM-H901, an adeno-associated viral (AAV) vector mediating FIX Padua (F9 [Arg338Leu]) gene transfer. This success follows multiple trials of AAV-mediated gene addition for haemophilia B that have adapted the FIX Padua transgene2–5 and demonstrate the therapeutic benefit of using an enhanced functional transgene for haemophilia gene therapy while also adapting lessons learned from previous work in AAV vector design.