Grant: Fellowship - Priority Announcement: Fanconi Anemia (SHOPP)

Blood transfusion is a critically important medical procedure, used to treat blood-loss due to trauma or during surgery, and also in the treatment of chronic blood disorders such as thalassemia, sickle-cell disease, or other forms of anemia. Over 15 million units (approx. 450mL per unit) are collected per year for preparation of blood products in Canada and the United States alone. Due to the presence of blood antigens, however, careful blood-typing is necessary to avoid adverse and sometimes fatal reactions that may result from a mismatched blood transfusion. The A and B blood antigens are considered the most clinically important blood antigens. People of blood-type O lack the A and B antigens on their red-blood-cells and thus are often considered "universal donors" (not accounting for minor antigens), yet units of type-O blood are frequently in short supply due to high demand. The use of enzymes to remove A and B antigens is a potential means of generating universal blood donor cells from blood types other than O. The recent discovery of an enzyme (of microbial origin) capable of removing both A and B antigens from red-blood-cells opens up a new approach for generating universal blood donor cells. The goal of this project is to develop the use of this enzyme, known as EABase, as a means to remove A and B antigens from red blood cells. Enzyme engineering, using "directed evolution" techniques, will be carried out to improve the efficiency of EABase in removing blood antigens. The ability to generate universal blood donor cells in such a way would be a breakthrough development, allowing transfusion without the need to find a positive match thus tremendously improving the supply of blood while increasing the safety of blood transfusions.