Chapter 13 - Hemophilia Gene Therapy

Abstract

Successful gene therapy for hemophilia B (factor IX deficiency) has been achieved. This has culminated after nearly 20years of basic and applied translational research. Improvements in vector technology, vector production, and an understanding of host immune response have facilitated positive outcomes in patients. New clinical trials using improved vector gene cassettes have begun that should yield even greater factor IX protein expression. Hemophilia has always been considered one of the bell-weather genetic disorders for the application of gene transfer due to the straightforward determination of endpoints: circulating blood factor levels and reduction of the bleeding phenotype as a direct consequence of increasing factor levels. In addition both factor IX and factor VIII proteins are not highly regulated and can be expressed in a variety of different tissues. Whereas a decade ago, increasing factor levels by 5% may have seemed a lofty goal, now there are expectations of achieving factor levels approaching that of normal individuals. In addition to the transfer of cDNAs, new methods for gene editing and gene repair loom on the horizon. In this review, we describe what led to these developments and considerations for the future.