Evidence map›Paper›PMID 27284167›Full record

ArticleScience (New York, N.Y.)2016

Molecular recordings by directed CRISPR spacer acquisition.

Seth L Shipman, Jeff Nivala, Jeffrey D Macklis, George M Church

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
17.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 246 citations in OpenAlex.

  1. Article
  2. Article
  3. Genomic repeats for single-cell molecular recording.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Seth L ShipmanDepartment of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Department of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Bauer Laboratory 103, Cambridge, MA 02138, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA.
Jeff NivalaDepartment of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA.
Jeffrey D MacklisDepartment of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Bauer Laboratory 103, Cambridge, MA 02138, USA.
George M ChurchDepartment of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA. gchurch@genetics.med.harvard.edu.
Harvard University · US

Funding

Causal Transcriptional Consequences of Human Genetic VariationP50HG005550 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2010 to 2014
$19.0M
Training in the Molecular Biology of Neurodegeneration and Alzheimer's DiseaseT32AG000222 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Bruce A YANKNER · 1992 to 2026
$18.5M
Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Recording neural activities onto DNAR01MH103910 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BOYDEN, EDWARD S., CHURCH, GEORGE M · 2013 to 2017
$9.5M
Molecular Controls over Neurogenesis, Subtype Development, and Diversity of Cortical Output Projection NeuronsR01NS045523 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MACKLIS, JEFFREY D · 2002 to 2020
$5.4M
NHGRI NIH HHS 5P50HG005550NHGRI NIH HHS RM1 HG008525NIA NIH HHS 5T32AG000222NIA NIH HHS T32 AG000222NIMH NIH HHS 5R01MH103910NIMH NIH HHS R01 MH103910NINDS NIH HHS 5R01NS045523NINDS NIH HHS R01 NS045523
6 · The paper itself

Abstract

The ability to write a stable record of identified molecular events into a specific genomic locus would enable the examination of long cellular histories and have many applications, ranging from developmental biology to synthetic devices. We show that the type I-E CRISPR (clustered regularly interspaced short palindromic repeats)-Cas system of Escherichia coli can mediate acquisition of defined pieces of synthetic DNA. We harnessed this feature to generate records of specific DNA sequences into a population of bacterial genomes. We then applied directed evolution so as to alter the recognition of a protospacer adjacent motif by the Cas1-Cas2 complex, which enabled recording in two modes simultaneously. We used this system to reveal aspects of spacer acquisition, fundamental to the CRISPR-Cas adaptation process. These results lay the foundations of a multimodal intracellular recording device.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGenome, BacterialCRISPR-Associated ProteinsDirected Molecular EvolutionEndodeoxyribonucleasesEndonucleasesEscherichia coli ProteinsSynthetic BiologyCas2 protein, E coliCRISPR-Associated ProteinsEndodeoxyribonucleasesEndonucleasesEscherichia coli ProteinsYgbT protein, E coli

Identifiers

PMID27284167
PMCPMC4994893
OpenAlexW2411492321

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.