Development of gene therapy for hemophilia: current states and future perspectives

Abstract

Hemophilia is congenital hemorrhagic disease due to genetic abnormality of blood coagulation factor VIII or factor IX. Hemophilia appears suitable for gene therapy because it is caused by a single gene abnormality, and therapeutic coagulation factor levels vary across a broad range. Since the success of gene therapy eliminates the need for regular administration of factor concentrates, the development has been met with great expectation from patients and their families. In fact, several clinical trials using adeno-associated virus (AAV) vectors have been started in Western countries, and long-term therapeutic effect could be obtained by single injection. More recently, the modifications of therapeutic gene and AAV serotypes have further improved therapeutic effects, and it appears to have reached the level of "cure". However, gene therapy using AAV vectors presents difficulties such as the existence of anti AAV capsid neutralizing antibody and hepatic injury due to cellular immunity with CD8+ T cells. Thus, it is essential to develop technologies adapted to a wide range of hemophilia patients, and to observe long-term safety and therapeutic effect after the gene therapy.