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Co-transcriptional RNA strand displacement circuits

View ORCID ProfileSamuel W. Schaffter, View ORCID ProfileElizabeth A. Strychalski
doi: https://doi.org/10.1101/2021.07.20.450530
Samuel W. Schaffter
1National Institute of Standards of Technology, Gaithersburg, MD 20899, USA
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  • For correspondence: samuel.schaffter@nist.gov
Elizabeth A. Strychalski
1National Institute of Standards of Technology, Gaithersburg, MD 20899, USA
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Abstract

Engineered molecular circuits that process information in biological systems could address emerging human health and biomanufacturing needs. However, such circuits can be difficult to rationally design and scale. DNA-based strand displacement reactions have demonstrated the largest and most computationally powerful molecular circuits to date but are limited in biological systems due to the difficulty in genetically encoding components. Here, we develop scalable co-transcriptional RNA strand displacement (ctRSD) circuits that are rationally programmed via base pairing interactions. ctRSD addresses the limitations of DNA-based strand displacement circuits by isothermally producing circuit components via transcription. We demonstrate the programmability of ctRSD in vitro by implementing logic and amplification elements, and multi-layer signaling cascades. Further, we show ctRSD kinetics are accurately predicted by a simple model of coupled transcription and strand displacement, enabling model-driven design. We envision ctRSD will enable rational design of powerful molecular circuits that operate in biological systems, including living cells.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/usnistgov/ctRSD-simulator

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted July 20, 2021.
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Co-transcriptional RNA strand displacement circuits
Samuel W. Schaffter, Elizabeth A. Strychalski
bioRxiv 2021.07.20.450530; doi: https://doi.org/10.1101/2021.07.20.450530
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Co-transcriptional RNA strand displacement circuits
Samuel W. Schaffter, Elizabeth A. Strychalski
bioRxiv 2021.07.20.450530; doi: https://doi.org/10.1101/2021.07.20.450530

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