Advances in gene therapy and genome editing therapy for hemophilia

Abstract

Hemophilia is an X-linked inherited bleeding disorder resulting from defects in the gene F8 (hemophilia A) or F9 (hemophilia B). Prophylaxis administration of coagulation factor concentrates is necessary to prevent joint bleeding in severe cases. Hemophilia is an attractive target for gene therapy owing to the monogenic nature and the easy evaluation of therapeutic coagulation factors in the blood. Currently, several clinical trials for hemophilia gene therapy have been conducted. Most of them are using the adeno-associated viral (AAV) vectors to transduce the genes of coagulation factors into the liver. A single administration of AAV vectors maintains the therapeutic levels of the coagulation factors over a long period, improving the bleeding rate, consumption of factor concentrates, and quality of life (QOL). On the other hand, the application of gene therapy using AAV vectors is limited to adult patients because their therapeutic effect is diminished by cell division. Therefore, the genome editing approach has attracted much attention because it can provide a permanent therapeutic effect from childhood. Indeed, a clinical trial that uses the AAV vector to deliver a genome-editing tool to the liver has been conducted. To apply gene therapy as a general medical care in the future, long-term observations of efficacy and safety, as well as discussion about its high medical costs, are essential.