Improving Enzymatic Removal of Major Blood Antigens

Blood transfusion is a critically important medical procedure used to treat blood loss due to trauma or during surgery; it is also used in the treatment of chronic blood disorders such as thalassemia, sickle-cell disease and other forms of anemia. Due to the presence of blood antigens, however, careful blood typing is necessary to avoid the adverse and sometimes fatal reactions that may result from a mismatched blood type during transfusion. The A and B blood antigens are considered the most clinically important blood antigens. These antigens consist of carbohydrate (sugar) molecules attached to the surface of blood cells. People with type O blood 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. Dr. David Kwan's research aims to investigate methods for the enzymatic removal of blood antigens from blood cells. Although enzymes that remove the A or B antigens to convert red blood cells have been discovered, they have low efficacy. Recently a new enzyme called EABase was discovered, which can efficiently remove the B antigen but only slowly removes the A antigen from red blood cells. The primary focus of Dr. Kwan's work will be to engineer the EABase enzyme using ""directed evolution"" techniques to improve the efficiency of EABase in removing blood antigens so that it may be a more efficient catalyst for the conversion of A-, B- and AB-type red blood cells into ""universal blood cells."" A secondary focus, in collaboration with the Centre for Blood Research, will test the use of polymer additives to enhance the rate of enzyme action. Over 15 million units (approximately 450 ml per unit) are collected for preparation of blood products in Canada and the United States per year. The ability to generate universal blood donor cells would be a breakthrough development, allowing transfusion without the need to find a positive match and tremendously improving the supply of blood while increasing the safety of blood transfusions.