Genetic programs can be compressed and autonomously decompressed in live cells

ABSTRACT Fundamental computer science concepts have inspired novel information-processing molecular systems in test tubes1,2,3,4,5,6,7,8,9,10,11,12,13 and genetically encoded circuits in

live cells14,15,16,17,18,19,20,21. Recent research has shown that digital information storage in DNA, implemented using deep sequencing and conventional software, can approach the maximum

Shannon information capacity22 of two bits per nucleotide23. In nature, DNA is used to store genetic programs, but the information content of the encoding rarely approaches this maximum24.

We hypothesize that the biological function of a genetic program can be preserved while reducing the length of its DNA encoding and increasing the information content per nucleotide. Here we

support this hypothesis by describing an experimental procedure for compressing a genetic program and its subsequent autonomous decompression and execution in human cells. As a test-bed we

choose an RNAi cell classifier circuit25 that comprises redundant DNA sequences and is therefore amenable for compression, as are many other complex gene circuits15,18,26,27,28. In one

example, we implement a compressed encoding of a ten-gene four-input AND gate circuit using only four genetic constructs. The compression principles applied to gene circuits can enable

fitting complex genetic programs into DNA delivery vehicles with limited cargo capacity, and storing compressed and biologically inert programs in vivo for on-demand activation. Access

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A TIME-RESOLVED, MULTI-SYMBOL MOLECULAR RECORDER VIA SEQUENTIAL GENOME EDITING Article Open access 06 July 2022 GENETIC CIRCUIT DESIGN AUTOMATION WITH CELLO 2.0 Article 23 February 2022

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Article  Google Scholar  Download references ACKNOWLEDGEMENTS The research was funded by the National Institutes of Health award 5R01CA155320 and by ETH Zürich. We thank B. Angelici for

discussions and E. Shapiro for commenting on the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland

Nicolas Lapique & Yaakov Benenson Authors * Nicolas Lapique View author publications You can also search for this author inPubMed Google Scholar * Yaakov Benenson View author

publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS N.L. conceived research, performed experiments, analysed data, and wrote the paper. Y.B. conceived

research, analysed data, supervised the project, and wrote the paper. CORRESPONDING AUTHOR Correspondence to Yaakov Benenson. ETHICS DECLARATIONS COMPETING INTERESTS The original miRNA

circuit technology is protected by patents awarded to Y.B. and co-inventors (US patent no. 9458509). The output delay technology is pending, with N.L. and Y.B. listed as co-inventors.

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GENETIC PROGRAMS CAN BE COMPRESSED AND AUTONOMOUSLY DECOMPRESSED IN LIVE CELLS LIFE SCIENCES REPORTING SUMMARY RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Lapique, N., Benenson, Y. Genetic programs can be compressed and autonomously decompressed in live cells. _Nature Nanotech_ 13, 309–315 (2018).

https://doi.org/10.1038/s41565-017-0004-z Download citation * Received: 27 June 2017 * Accepted: 19 September 2017 * Published: 13 November 2017 * Issue Date: April 2018 * DOI:

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