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Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components

Thubagere, Anupama J. and Thachuk, Chris and Berleant, Joseph and Johnson, Robert F. and Ardelean, Diana A. and Cherry, Kevin M. and Qian, Lulu (2017) Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components. Nature Communications, 8 . Art. No. 14373. ISSN 2041-1723. PMCID PMC5331218. doi:10.1038/ncomms14373.

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Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits.

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URLURL TypeDescription CentralArticle
Thachuk, Chris0000-0001-5913-1732
Berleant, Joseph0000-0001-5672-4292
Qian, Lulu0000-0003-4115-2409
Additional Information:© The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit Received 7 Aug 2016 | Accepted 21 Dec 2016 | Published 23 Feb 2017. A.J.T. was supported by an NSF grant (1351081) and an NSF expedition in computing (1317694). C.T. was supported by a Banting Fellowship. L.Q. was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund (1010684) and a Faculty Early Career Development Award from NSF (1351081). All other authors were supported by Innovation in Education funds from the Provost’s Office at the California Institute of Technology, through a class BE/CS 196—Design and Construction of Programmable Molecular Systems. Data availability: Key data supporting the findings of this study are available to download at the Seesaw Compiler website and all other data are available from the corresponding author upon reasonable request. Author Contributions: C.T. designed the logic circuit. C.T., J.B., R.F.J. and D.A.A. designed the DNA circuit, performed the experiments and analysed the data of the rule 124 sub-circuit. K.M.C. designed and performed the experiments, and analysed the data for gate calibration. A.J.T. designed and performed the experiments and analysed the data of the full circuit and led the project to completion. C.T. and L.Q. developed the model. A.J.T., C.T. and L.Q. wrote the manuscript. L.Q. initiated and guided the project. The authors declare no competing financial interests.
Funding AgencyGrant Number
Banting FellowshipUNSPECIFIED
Burroughs Wellcome Fund1010684
PubMed Central ID:PMC5331218
Record Number:CaltechAUTHORS:20170223-142901132
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Official Citation:Thubagere, A. J. et al. Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components. Nat. Commun. 8, 14373 doi: 10.1038/ncomms14373 (2017).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74509
Deposited By: George Porter
Deposited On:23 Feb 2017 23:42
Last Modified:04 Apr 2022 17:04

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