Chapter 10. Gene Therapy for Haemophilia

Summary

Haemophilia results from the absence of one factor in the blood clotting cascade and, in theory, gene therapy could completely cure the disease. Retroviral vectors have been used to transfer the Factor VIII gene into various cell types, including fibroblasts, myoblasts and haemopoietic stem cells, resulting in the secretion of functional protein. Transient expression in vivo has been attained after implantation of transfected fibroblasts in nude mice. Adenoviral vectors have also been used in animal studies of Factor VIII. For haemophilia B, there have been parallel developments with Factor IX, using retroviral and adenoviral vectors, as well as adeno-associated virus, which infects quiescent cells and is thus important for gene transfer to the liver. While proof-of-principle has been demonstrated, improvements are needed in cell isolation, gene transfer, cell transplantation, gene expression and gene targeting to the desired tissue in vivo.