Programming cell-free biosensors with DNA strand displacement circuits.

Nat Chem Biol

Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA.

Published: April 2022

Cell-free biosensors are powerful platforms for monitoring human and environmental health. Here, we expand their capabilities by interfacing them with toehold-mediated strand displacement circuits, a dynamic DNA nanotechnology that enables molecular computation through programmable interactions between nucleic acid strands. We develop design rules for interfacing a small molecule sensing platform called ROSALIND with toehold-mediated strand displacement to construct hybrid RNA-DNA circuits that allow fine-tuning of reaction kinetics. We use these design rules to build 12 different circuits that implement a range of logic functions (NOT, OR, AND, IMPLY, NOR, NIMPLY, NAND). Finally, we demonstrate a circuit that acts like an analog-to-digital converter to create a series of binary outputs that encode the concentration range of the molecule being detected. We believe this work establishes a pathway to create 'smart' diagnostics that use molecular computations to enhance the speed and utility of biosensors.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964419PMC
http://dx.doi.org/10.1038/s41589-021-00962-9DOI Listing

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