Research Project
3501239
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 treatment of 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.
