Portal de Periódicos da CAPES

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

2022; National Academy of Sciences; Volume: 119; Issue: 18 Linguagem: Inglês

10.1073/pnas.2112979119

1091-6490

Johan O. L. Andreasson, Michael R. Gotrik, Michelle J. Wu, Hannah K. Wayment-Steele, Wipapat Kladwang, Fernando Gutiérrez Pórtela, Roger Wellington-Oguri, Rhiju Das, William J. Greenleaf,

Bacteriophages and microbial interactions

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.