GENETIC ENGINEERING OF AN IMPROVED FACTOR VIII PRODUCT

FACTOR VIII IS THE PLASMA PROTEIN THAT IS FUNCTIONALLY DEFICIENT IN HEMOPHILIA A PATIENTS, RESULTING IN THE CLINICAL BLEEDING DISORDER. PATIENTS WITH THIS DISEASE REQUIRE FREQUENT INFUSIONS OF FACTOR VIII IN ORDER TO MAIN- TAIN HEMOSTASIS, PARTICULARLY DURING SURGERY OR FOLLOWING PHYSICAL TRAUMA. PRESENTLY, THE COMMERCIAL FACTOR VIII PRODUCT IS PURIFIED FROM POOLED BLOOD PLASMA OBTAINED FROM HUMAN DONORS. RECENT DEVELOPMENTS HAVE MADE IT POSSIBLE TO PRODUCE COMMERCIALLY VIABLE AMOUNTS OF FACTOR VIII USING RECOMBINANT HOST/VECTOR SYSTEMS. THE PRODUCT FROM SUCH A PRODUCTION SCHEME SHOULD HAVE SUBSTANTIALLY IMPROVED PROP- ERTIES RELATIVE TO THE PLASMA-DERIVED PRODUCT. THESE INCLUDE HIGHER PURITY, LOWER VOLUMES, AND MARKEDLY REDUCED RISKS OF VIRAL CONTAMINATION. THE AIM OF THE PROPOSED RESEARCH PLAN IS TO GENETICALLY MODIFY THE FACTOR VIII PROTEIN TO FURTHER IMPROVE ITS PHARMACOLOGIC UTILITY WHILE REDUCING THE COST OF TREATMENT USING RECOMBINANT DNA TECHNOLOGIES.