Towards gene therapy for hemophilia B.
Hemophilia B is an X-chromosome-linked bleeding disorder resulting from lack of clotting factor IX activity and affects about 1 in 30,000 males. Current therapy involves injection of crude factor IX prepared from pooled human plasma. Treatment is complicated by viral contaminants in factor IX preparations, such as non A-non B hepatitis and the AIDS virus, and by the practical difficulties of chronic injections. An alternative therapy might include the insertion of a factor IX expression vector into the somatic cells of affected individuals to allow continued production of factor IX. Toward this end, we have constructed a retrovirus vector for transfer and expression of factor IX. Despite the fact that factor IX is normally synthesized in hepatocytes and requires extensive post-translational modification for activity, we have shown that fully active factor IX can be made by human skin-derived fibroblasts. These results open the way to testing the use of skin grafts for gene therapy of hemophilia B.
D001681:Biological Assay; D002478:Cells, Cultured; D005164:Factor IX / Q000235:genetics*; D005818:Genetic Engineering; D005822:Genetic Vectors; D002836:Hemophilia B / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics
D005164:Factor IX; D007041:Hypoxanthine Phosphoribosyltransferase