PT  - JOURNAL ARTICLE
AU  - Samuel W. Schaffter
AU  - Elizabeth A. Strychalski
TI  - Co-transcriptional RNA strand displacement circuits
AID  - 10.1101/2021.07.20.450530
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.20.450530
4099  - http://biorxiv.org/content/early/2021/07/20/2021.07.20.450530.short
4100  - http://biorxiv.org/content/early/2021/07/20/2021.07.20.450530.full
AB  - 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 StatementThe authors have declared no competing interest.