251. Towards gene therapy for hemophilia B.
- Author
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Anson DS, Hock RA, Austen D, Smith KJ, Brownlee GG, Verma IM, and Miller AD
- Subjects
- Biological Assay, Cells, Cultured, Genetic Engineering, Genetic Vectors, Hemophilia B genetics, Humans, Hypoxanthine Phosphoribosyltransferase genetics, Factor IX genetics, Hemophilia B therapy
- Abstract
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.
- Published
- 1987