Cited by 298Gene Regulatory Network AnalysisCRISPR and Genetic EngineeringAdvanced biosensing and bioanalysis techniques

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

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Farzadfard, Fahim, Lu, Timothy K.·2014·Science

Abstract

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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  • Preservation of DNA digital archives can be implemented using not only in vitro substrates but also in vivo approaches.

    “It is also important to mention that the preservation of DNA digital archives can be implemented using not only in vitro substrates but also in vivo approaches.150−153”
  • Amplified material was pure and ready for re-encapsulation into silica particles, which could be re-introduced directly back into the data pool and thereby represents a complete write-store-access-read cycle that in principle may be applied to larger-scale datasets, with periodic renewal of single-stranded DNA barcodes and bacterial replication of DNA data following reading.

    “Amplified material was pure and ready for re-encapsulation into silica particles, which could be re-introduced directly back into the data pool and thereby represents a complete write-store-access-read cycle that in principle may be applied larger-scale datasets, with periodic renewal of single-stranded DNA barcodes and bacterial replication of DNA data following reading25–27.”

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Authors
Farzadfard, F., & Lu, T. K.
Affiliations
Massachusetts Institute of Technology (US)
Corresponding author
Lu, Timothy K.
Venue
Science
Published
2014-11-14
Volume
346
Issue
6211
Pages
1256272-1256272
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2065515388
Cited by
298
References
61
Citations by year
2026: 17 · 2025: 23 · 2024: 24 · 2023: 20 · 2022: 30 · 2021: 26 · 2020: 24 · 2019: 26 · 2018: 27 · 2017: 26 · 2016: 29 · 2015: 23 · 2014: 3
FWCI
11.08
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • PMC
Funders
  • National Institutes of Health (1dp2od008435-01)
  • National Institute of General Medical Sciences (P50GM098792)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
Keywords
cellular memory, analog memory, single-stranded DNA, recombinases, genome editing
MeSH terms
Base Sequence, Cells, DNA, Single-Stranded, Escherichia coli, Genetic Code, Memory, Molecular Sequence Data, Tape Recording, Transcription, Genetic, Writing, Information Storage and Retrieval, Genomics, Bioengineering, Synthetic Biology

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