Crowdsourced RNA design discovers diverse, reversible, efficient, self-contained molecular switches

Internet-based scientific communities promise a means to apply distributed, diverse human intelligence toward previously intractable scientific problems. However, current implementations have not allowed communities to propose experiments to test all emerging hypotheses at scale or to modify hypotheses in response to experiments. We report high-throughput methods for molecular characterization of nucleic acids that enable the large-scale video game-based crowdsourcing of RNA sensor design, followed by high-throughput functional characterization. Iterative design testing of thousands of crowdsourced RNA sensor designs produced near-thermodynamically optimal and reversible RNA switches that act as self-contained molecular sensors and couple five distinct small molecule inputs to three distinct protein binding and fluorogenic outputs. This work suggests a paradigm for widely distributed experimental bioscience.

Automated summary

This research presents high-throughput methods for molecular characterization of nucleic acids, enabling crowdsourcing of RNA sensor design and functional testing. Iterative design testing of thousands of crowdsourced RNA sensor designs resulted in near-thermodynamically optimal and reversible RNA switches that couple small molecule inputs to protein binding and fluorogenic outputs. This work proposes a paradigm for widely distributed experimental bioscience.