MEMBRANE IMMUNOAFFINITY PURIFICATION OF FACTOR VIII:C

HEMOPHILIA A IS AN INHERITED BLEEDING DISORDER THAT STEMS FROM LACK OF COAGULATION FACTOR VIII:C (F.VIII:C). CRUDE PREPARATIONS OF PLASMA-DERIVED FACTOR VIII USED IN TREATMENTOF HEMOPHILIA ARE IN SHORT SUPPLY WORLDWIDE AND CARRY THE RISK OF VIRAL DISEASE TRANSMISSION. ALTHOUGH ULTRAPURIFIED F.VIII:C CAN BE PREPARED IN SMALL QUANTITIES USING IMMUNOAFFINITY COLUMN CHROMATOGRAPHY, CONVENTIONAL AFFINITY SEPARATIONS TECHNOLOGY IS NOT SUITED TO LARGE SCALE PRODUCTION OF PURIFIED F.VIII:C. THE OBJECTIVE OF THE PROPOSED RESEARCH IS TO DEVELOP A MEMBRANE-BASED AFFINITY PROCESS FOR PURIFICATION OF F.VIII:C DIRECTLY FROM BLOOD PLASMA THAT EMPLOYS METHODOLOGIES ESTABLISHED FOR THE COLUMN-BASED PROCEDURE. IN CONTRAST TO CONVENTIONAL TECHNOLOGIES, WE EXPECT THAT MEMBRANE AFFINITY PROCESSES WILL BE AMENABLE TO INDUSTRIAL OPERATIONS. IN PHASE I, A KNOWLEDGE BASE WILL BE ESTABLISHED THAT WILL PERMIT THE RATIONAL DESIGN OF HOLLOW FIBER MEMBRANE MODULES FOR IMMUNOAFFINITY PURIFICATION OF F.VIII:C. IN PHASE II, PROTOTYPE AFFINITY MODULES WILL BE CONSTRUCTED AND PURIFIED F.VIII:C WILL BE TESTED FOR SAFETY AND EFFICACY IN ANIMALS. THE PURPOSE OF THIS PROJECT IS TO ESTABLISH THE TECHNICAL BASIS FOR MEMBRANE-MEDIATED AFFINITY PURIFICATION OF F.VIII:C, TO DEVELOP A GENERAL APPROACH TO INDUSTRIAL AFFINITY SEPARATIONS, AND TO IMPROVE THE QUALITY OF LIFE OF INDIVIDUALS CURRENTLY UNDERGOING FACTOR VIII REPLACEMENT THERAPY.