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Cotranscriptionally encoded RNA strand displacement circuits

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 computat...

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Autores principales: Schaffter, Samuel W., Strychalski, Elizabeth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942360/
https://www.ncbi.nlm.nih.gov/pubmed/35319994
http://dx.doi.org/10.1126/sciadv.abl4354
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author Schaffter, Samuel W.
Strychalski, Elizabeth A.
author_facet Schaffter, Samuel W.
Strychalski, Elizabeth A.
author_sort Schaffter, Samuel W.
collection PubMed
description 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 cotranscriptionally encoded RNA strand displacement (ctRSD) circuits that are rationally programmed via base pairing interactions. ctRSD circuits address the limitations of DNA-based strand displacement circuits by isothermally producing circuit components via transcription. We demonstrate circuit programmability in vitro by implementing logic and amplification elements, as well as multilayer cascades. Furthermore, we show that circuit kinetics are accurately predicted by a simple model of coupled transcription and strand displacement, enabling model-driven design. We envision ctRSD circuits will enable the rational design of powerful molecular circuits that operate in biological systems, including living cells.
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spelling pubmed-89423602022-04-04 Cotranscriptionally encoded RNA strand displacement circuits Schaffter, Samuel W. Strychalski, Elizabeth A. Sci Adv Physical and Materials Sciences 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 cotranscriptionally encoded RNA strand displacement (ctRSD) circuits that are rationally programmed via base pairing interactions. ctRSD circuits address the limitations of DNA-based strand displacement circuits by isothermally producing circuit components via transcription. We demonstrate circuit programmability in vitro by implementing logic and amplification elements, as well as multilayer cascades. Furthermore, we show that circuit kinetics are accurately predicted by a simple model of coupled transcription and strand displacement, enabling model-driven design. We envision ctRSD circuits will enable the rational design of powerful molecular circuits that operate in biological systems, including living cells. American Association for the Advancement of Science 2022-03-23 /pmc/articles/PMC8942360/ /pubmed/35319994 http://dx.doi.org/10.1126/sciadv.abl4354 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Physical and Materials Sciences
Schaffter, Samuel W.
Strychalski, Elizabeth A.
Cotranscriptionally encoded RNA strand displacement circuits
title Cotranscriptionally encoded RNA strand displacement circuits
title_full Cotranscriptionally encoded RNA strand displacement circuits
title_fullStr Cotranscriptionally encoded RNA strand displacement circuits
title_full_unstemmed Cotranscriptionally encoded RNA strand displacement circuits
title_short Cotranscriptionally encoded RNA strand displacement circuits
title_sort cotranscriptionally encoded rna strand displacement circuits
topic Physical and Materials Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942360/
https://www.ncbi.nlm.nih.gov/pubmed/35319994
http://dx.doi.org/10.1126/sciadv.abl4354
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