Extensive efforts to develop a safe and effective method of gene therapy for hemophilia A have not met with success. In this project the applicant will test a promising ex vivo approach to delivering factor VIII using a recently identified population of cells called blood outgrowth endothelial cells or BOEC. The principal investigator has shown that engineered BOEC may safely be used to provide sustained, therapeutic Levels of fVIII in a mouse model of hemophilia A. The Specific Aim of this project is to demonstrate that engineered BOEC can be used to achieve therapeutic levels of canine coagulation factor VIII in the hemophilia A dog. In this study, BOEC will be obtained from two hemophilia A dogs, transfected with fVIII and infused into the same animals. Coagulation factor VIII levels will be assayed over time. If therapeutic levels are detected, cuticle bleed times will also be determined. If, as expected, affirmative results are obtained in this study, the applicant intends to pursue a full preclinical development plan for the BOEC technology and to file an IND for the hemophilia A indication. PROPOSED COMMERCIAL APPLICATION: BOEC represent a novel platform technology for gene therapy and other medical applications. Success in this and subsequent studies could lead to the ultimate approval of BOEC technology as a preferred therapy for hemophila A and other indications.
Thesaurus Terms: coagulation factor VIII, gene delivery system, gene therapy, hemophilia A, technology /technique development blood cell, recombinant DNA dog, enzyme linked immunosorbent assay, tissue /cell culture, transfection /expression vector, western blotting
