Current treatment regimes for Haemophilia A involve the frequent administration of plasma derived or recombinant human Factor VIII (hFVIII). However, treatment is restricted by the availability, short half-life and high cost of purifled hFVIII. Therefore, we propose to develop a clinical gene therapy protocol suitable for the treatment of patients suffering from Haemophilia A.
To achieve this we propose to assess a number of eukaryotic promoters for cell type specificity in addition to persistence of on in lineages derived from hematopoietic stem cells. These promoters will then be transferred into a retroviral backbone where they will regulate expression of the hFVIII cDNA. Hematopoietic cells will be obtained from patients bone marrow, transduced in vitro, prior to reimplantation into the patients. Peripheral blood cells derived from the transduced hematopoietic stem cells are expected to secrete hFvIII directly into the plasma resulting in the systemic correction of the condition.