New and improved AAVenues: current status of hemophilia B gene therapy

Abstract

Introduction: Hemophilia B is a sex linked, monogenic, coagulation disorder caused by a deficiency in functional factor IX protein. Gene therapy for this disorder via systemic administration of an adeno-associated virus (AAV) encoding an optimized factor IX construct has shown considerable success, ameliorating the bleeding phenotype in a number of patients. However challenges to sustained curative gene transfer in this patient population remain, and as such there are efforts in the field to improve long term factor IX expression, via optimisations to the AAV vector, transgene cassette and correction strategy.

Areas covered: In this article we review the current state of AAV mediated gene therapy for hemophilia B in the clinic, detail progress since the first successful trial, and discuss alternative approaches from the AAV gene therapy field.

Expert opinion: AAV mediated gene therapy for hemophilia B is safe and efficacious; however, to achieve gene therapy success on a global scale, improvements to large scale production and alternative AAV serotype approaches need to be designed. With the current means of AAV gene therapy treatment entering the market concomitantly with the advent of long half-life clotting factor products, the quality of life for hemophilia patients worldwide is likely to improve significantly.

Keywords: AAV; FIX; adeno-associated virus; coagulopathy; factor IX; gene delivery; gene therapy; hemophilia; serotype.