Kizhakkedathu team makes breakthrough toward developing universal O donor RBCs

Optimizing cell-surface biological reactions is an important goal of biotechnology and industrial processes. In a report published this month in Nature Communications, CBR researchers, led by Dr. Jay Kizhakkedathu, describes the development of a robust and universal technique to greatly enhance the rates of cell surface reactions and interactions by means of macromolecular crowding. In the article, Raf Chapanian et al. demonstrate the practical utility of this enhancement technology by efficient enzymatic conversion of A, B and AB red blood cells to universal (O) donor red blood cellsat physiological pH and at room temperature. By use of macromolecular crowders they have remarkably reduced the amounts of enzyme required for such conversions by more than 400-fold. The underlying mechanism of this phenomenon on the cell surface was probed primarily through the use of a range of confocal microscopy experiments.

A major impediment to the application of macromolecule-based cell-surface engineering is the requirement for large amounts of reagents due to the low levels of their association with the cell surface. The Kizhakkedathu group, in collaboration with Dr. Steve Withers’ group in Chemistry, were able to use relatively inexpensive, cell compatible, neutral polymers such as dextran and ficoll, as macromolecular crowders, yielding a method for enhancing cell-surface enzymatic activity that may be widely applied.

This highly relevant research was funded from several sources, including the Canadian Blood Services, the CIHR, NSERC, Health Canada, and the CBR.