Imagine if there were drugs that could optimize their dose in real-time, leading to better patient outcomes. Cellular factories that could self-regulate their metabolism, enabling sustainable chemical production. Gene editing tools that could target specific cells, reducing toxic off-target effects. The key to realizing those technological advances, according to University of Washington molecular engineering alums Jason Fontana and David Sparkman-Yager, is RNA.
RNA is a molecule with many functions in the cell, from coding proteins to catalyzing chemical reactions. One type of RNA molecule, called an aptamer, detects molecules with high affinity and specificity, similar to how an antibody binds an antigen. In nature, cells use RNA aptamers like sensors to monitor their environment and respond in real time; for example, they can modulate gene expression as a result of changes in the local concentration of small effector molecules.
If scientists could dictate which molecules RNA aptamers bind to, and how the cell responds, they could engineer biology to solve complex problems.
Fontana and Sparkman-Yager have developed a computational platform that allows them to do just that. Their technology is based on research they conducted for their theses under chemical engineering professor James Carothers, and chemistry professor Jesse Zalatan. In January 2021, they started a company, Wayfinder Biosciences, to apply this platform to everything from sustainable biomanufacturing to targeted therapeutics.
“We’ve figured out how to design RNA so that we can control how biology responds, on demand, to the molecules we choose,” said Fontana, who received his Ph.D. in molecular engineering in 2020. “Basically, we pair RNA aptamers with another piece of RNA that does something useful, such as producing a measurable output like light or activating a guide RNA to induce gene editing, only when the aptamer binds its target.”
