Letter

CRISPR–Cas encoding of a digital movie into the genomes of a population of living bacteria

  • Nature volume 547, pages 345349 (20 July 2017)
  • doi:10.1038/nature23017
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Abstract

DNA is an excellent medium for archiving data. Recent efforts have illustrated the potential for information storage in DNA using synthesized oligonucleotides assembled in vitro1,2,3,4,5,6. A relatively unexplored avenue of information storage in DNA is the ability to write information into the genome of a living cell by the addition of nucleotides over time. Using the Cas1–Cas2 integrase, the CRISPR–Cas microbial immune system stores the nucleotide content of invading viruses to confer adaptive immunity7. When harnessed, this system has the potential to write arbitrary information into the genome8. Here we use the CRISPR–Cas system to encode the pixel values of black and white images and a short movie into the genomes of a population of living bacteria. In doing so, we push the technical limits of this information storage system and optimize strategies to minimize those limitations. We also uncover underlying principles of the CRISPR–Cas adaptation system, including sequence determinants of spacer acquisition that are relevant for understanding both the basic biology of bacterial adaptation and its technological applications. This work demonstrates that this system can capture and stably store practical amounts of real data within the genomes of populations of living cells.

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Acknowledgements

S.L.S. is a Shurl and Kay Curci Foundation Fellow of the Life Sciences Research Foundation. The project was supported by grants from the National Institute of Mental Health (5R01MH103910), National Human Genome Research Institute (5RM1HG008525), and Simons Foundation Autism Research Initiative (368485) to G.M.C., the National Institute of Neurological Disorders and Stroke (5R01NS045523) to J.D.M and an Allen Distinguished Investigator Award from the Paul G. Allen Frontiers Group to J.D.M. We thank G. Kuznetsov for comments on the manuscript.

Author information

Affiliations

  1. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA

    • Seth L. Shipman
    • , Jeff Nivala
    •  & George M. Church
  2. Department of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Bauer Laboratory 103, Cambridge, Massachusetts 02138, USA

    • Seth L. Shipman
    •  & Jeffrey D. Macklis
  3. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA

    • Seth L. Shipman
    • , Jeff Nivala
    •  & George M. Church

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Contributions

S.L.S. and J.N. conceived the study. S.L.S. designed the work, performed experiments, analysed data, wrote custom Python analysis software, and wrote the manuscript with input from J.N., J.D.M. and G.M.C. S.L.S. J.N., J.D.M. and G.M.C. discussed results and commented on the manuscript.

Competing interests

S.L.S. J.N, J.D.M., and G.M.C. are inventors on a provisional patent (62/296,812) filed by the President and Fellows of Harvard College that covers the work in this manuscript. A complete accounting of the financial interests of G.M.C. is listed at: http://arep.med.harvard.edu/gmc/tech.html.

Corresponding author

Correspondence to George M. Church.

Reviewer Information Nature thanks R. Barrangou and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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