Current projects center on the use of viral vector gene transfer systems to correct inherited hematologic disorder such as hemoglobinopathies (sickle cell disease and thalassemia), bone marrow failure (Fanconi's anemia), and immunodeficiency states (severe combined immunodeficiency, SCID). Retroviral and adeno-associated viral (rAAV) vectors have been constructed containing the Fanconi complementing group C gene (FACC). Phenotypic correction of several individual mutant FACC lymphoblast cell lines was documented following gene transduction with recombinant virus. Primitive hematopoietic CD34+ cells isolated from a patient carrying a disease-associated mutation were transduced and correction of the defect measured by in vitro colony growth. In vivo gene transduction using the FACC-retrovirus marked murine bone marrow, spleen and peripheral blood cells. These results serve as the pre-clinical data for a human gene therapy trial which has been approved by the RAC and is awaiting by the FDA.
