(Investigator s abstract) Hemophilia is a sex linked recessive disorder caused by a deficiency of blood coagulation factors VIII or IX. Several features make hemophilia an attractive target for gene therapy. First, the levels of factors VIII and IX are not regulated so small increases in the level of either clotting factor would have important effects on bleeding symptoms. Second, as a sex-linked disorder, correction of only one gene is required. Third, much is known about the structure, function and gene analysis of both molecules. Fourth, well established animal models are available for pre-clinical studies. Finally, hemophilia is a relatively common genetic disorder with nearly 20,000 cases in the United States. Despite the attractiveness of hemophilia as a target for gene therapy and encouraging initial studies, the promise of gene therapy remains unfulfilled. Problems with vector delivery, DNA integration and protein expression persist. The purpose of this conference will be to assemble as completely as possible, laboratories pursuing gene therapy research in hemophilia and to focus these groups on current issues in vector development, immune response to transduced gene products and current clinical models for gene therapy. The overall goal of the proposal will be to encourage communication between groups with an eye on problem solving.
