Ewan K.S. McRae, Ph.D.

Research

My research focus is on designing stable, controllable therapeutic RNAs. Vaccines that harness RNA have been shown to produce a protein that can trigger a robust protective immune response. These vaccines, however, are made less effective by the rapid degradation of linear RNAs, requiring delivery of higher doses that could lead to possible side effects. Using circular forms of RNA would circumvent this stability issue, producing vaccines that are effective in smaller doses. These RNA loops, however, must include a ribosome-binding element—a recognition sequence that directs protein-synthesizing ribosomes where to attach. Combining cutting-edge methods in cell and molecular genetics, bioengineering, and synthetic and computational biology, my group will screen a library of different ribosome-binding elements to isolate those that direct the most efficient synthesis of a reporter protein. We will then redesign these elements to include a customized sequence that will act as an on/off switch when exposed to a “trigger RNA.” This work will provide a strategy for designing more effective RNA therapeutics and vaccines that can be programmed to target particular cells or tissues.