Hemophilia Gene Therapy; Clinical and Molecular Aspects

Hemophilia is a coagulation disorder in which bleeding time is prolonged. There are a number of hemophilia subtypes and more than 4,000,000 individuals are suffered worldwide. The most common types of hemophilia are type A and B in which coagulation factor VIII and IX are defected respectively. Type A hemophilia is responsible for 80% to 85% of cases. The genes of 8 and 9 coagulation factors located on the long arm of X chromosome and mutation in these genes causes disturbance in coagulation. This disease is a very good target for gene therapy because if amount of protein production reaches 1% that of normal the disease phenotype is modified. Different methods of hemophilia gene therapy include increased production of coagulation factors via insertion of attributed genes into patient’s stem cells by vectors, or insertion of transgenes into differentiated cells with prolonged survival such as muscle or liver cells. One of the most recent advances in hemophilia gene therapy is using induced pluripotent stem cells (iPS) for gene transfer. Hepatocytes are very good candidates for hemophilia gene therapy due to their natural capacity for production of coagulation factors. Myocytes are also suitable for injection of transgene because they are available and have sufficient secretory power. Most important and useful viral vectors for hemophilia are retroviral, lentiviral, and Adeno- Associated viruses. Amongthese only the retroviral vectors target dividing cells.