Genomically encoded analog memory with precise in vivo DNA writing in living cell populations

Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations a...

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Main Authors: Farzadfard, Fahim, Lu, Timothy K
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: American Association for the Advancement of Science (AAAS) 2016
Online Access:http://hdl.handle.net/1721.1/100835
https://orcid.org/0000-0003-1389-8203
https://orcid.org/0000-0002-9999-6690
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author Farzadfard, Fahim
Lu, Timothy K
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Farzadfard, Fahim
Lu, Timothy K
author_sort Farzadfard, Fahim
collection MIT
description Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations as genomic “tape recorders” for the analog and distributed recording of long-term event histories. We describe a platform for generating single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals. When coexpressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs. This platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies.
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spelling mit-1721.1/1008352022-10-01T17:22:24Z Genomically encoded analog memory with precise in vivo DNA writing in living cell populations Farzadfard, Fahim Lu, Timothy K Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Microbiology Graduate Program Massachusetts Institute of Technology. Research Laboratory of Electronics Massachusetts Institute of Technology. Synthetic Biology Center Farzadfard, Fahim Lu, Timothy K. Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations as genomic “tape recorders” for the analog and distributed recording of long-term event histories. We describe a platform for generating single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals. When coexpressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs. This platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies. National Institutes of Health (U.S.) (New Innovator Award 1DP2OD008435) National Centers for Systems Biology (U.S.) (Grant 1P50GM098792) United States. Office of Naval Research (N000141310424) United States. Defense Advanced Research Projects Agency 2016-01-14T17:18:30Z 2016-01-14T17:18:30Z 2014-11 2014-05 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/100835 Farzadfard, F., and T. K. Lu. “Genomically Encoded Analog Memory with Precise in Vivo DNA Writing in Living Cell Populations.” Science 346, no. 6211 (November 13, 2014): 1256272–1256272. https://orcid.org/0000-0003-1389-8203 https://orcid.org/0000-0002-9999-6690 en_US http://dx.doi.org/10.1126/science.1256272 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC
spellingShingle Farzadfard, Fahim
Lu, Timothy K
Genomically encoded analog memory with precise in vivo DNA writing in living cell populations
title Genomically encoded analog memory with precise in vivo DNA writing in living cell populations
title_full Genomically encoded analog memory with precise in vivo DNA writing in living cell populations
title_fullStr Genomically encoded analog memory with precise in vivo DNA writing in living cell populations
title_full_unstemmed Genomically encoded analog memory with precise in vivo DNA writing in living cell populations
title_short Genomically encoded analog memory with precise in vivo DNA writing in living cell populations
title_sort genomically encoded analog memory with precise in vivo dna writing in living cell populations
url http://hdl.handle.net/1721.1/100835
https://orcid.org/0000-0003-1389-8203
https://orcid.org/0000-0002-9999-6690
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