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 hypothe...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-05, Vol.119 (18), p.e2112979119-e2112979119
Main Authors: Andreasson, Johan O L, Gotrik, Michael R, Wu, Michelle J, Wayment-Steele, Hannah K, Kladwang, Wipapat, Portela, Fernando, Wellington-Oguri, Roger, Das, Rhiju, Greenleaf, William J
Format: Article
Language:English
Subjects:
Biological Sciences
Computer & video games
Crowdsourcing
Crowdsourcing - methods
Design
Hypotheses
Intelligence
Molecular machines
Nucleic acids
Physical Sciences
Ribonucleic acid
RNA
RNA - chemistry
RNA - genetics
Switches
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2112979119