Evidence map›Paper›PMID 30633905›Full record

ArticleCell2019

CRISPR-Cas9 Circular Permutants as Programmable Scaffolds for Genome Modification.

Benjamin L Oakes, Christof Fellmann, Harneet Rishi, Kian L Taylor, Shawn M Ren, Dana C Nadler, Rayka Yokoo, Adam P Arkin, Jennifer A Doudna, David F Savage

Abstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
–field-weighted citation impact
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

61 citing papers in PubMed.

  1. Systematic discovery of circular permutations across the protein universe using CIRPIN.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Embedded CRISPRi Enhances Gene-Silencing Efficiency in Drosophila.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Detection of circular permutations by Protein Language Models.Computational and structural biotechnology journal · 2025
    Article
  12. Article
  13. Engineered transcription-associated Cas9 targeting in eukaryotic cells.bioRxiv : the preprint server for biology · 2024
    Article
  14. Harnessing the evolving CRISPR/Cas9 for precision oncology.Journal of translational medicine · 2024
    Review
  15. Review
  16. Rational Design of a Circularly Permuted Flavin-Based Fluorescent Protein.Chembiochem : a European journal of chemical biology · 2024
    Article
  17. Article
  18. Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Benjamin L OakesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Christof FellmannDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Gladstone Institutes, San Francisco, CA 94158, USA.
Harneet RishiGraduate Group in Biophysics, University of California, Berkeley, Berkeley, CA 94720, USA.
Kian L TaylorInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Shawn M RenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Dana C NadlerDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Rayka YokooDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Adam P ArkinDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Jennifer A DoudnaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Graduate Group in Biophysics, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
David F SavageDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: savage@berkeley.edu.

Funding

GENOMICST32HG000047 · NHGRI · UNIVERSITY OF CALIFORNIA BERKELEY · PI RASMUS NIELSEN, Daniel Soleyman Rokhsar · 2000 to 2026
$13.5M
Fluorescent biosensors for metabolite imaging in live cellsDP2EB018658 · NIBIB · UNIVERSITY OF CALIFORNIA BERKELEY · PI SAVAGE, DAVID FRANK · 2013 to 2013
$2.2M
Engineering CRISPR-Cas proteins for conditional and robust interrogation of the genomeR01GM127463 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI SAVAGE, DAVID FRANK · 2019 to 2022
$1.2M
Mechanism and Therapeutic Application of RNA-Guided Immune SystemsR00GM118909 · NIGMS · J. DAVID GLADSTONE INSTITUTES · PI FELLMANN, CHRISTOF · 2018 to 2020
$747k
Genome Sequencer FLXS10RR029668 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI NGAI, JOHN J. · 2010 to 2010
$623k
Illumina Sequencer to Facilitate Functional Genomics at BerkeleyS10RR027303 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI TAYLOR, JOHN W. · 2010 to 2010
$500k
Mechanism and therapeutic application of RNA-guided immune systemsK99GM118909 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI FELLMANN, CHRISTOF · 2016 to 2017
$180k
Howard Hughes Medical InstituteNCRR NIH HHS S10 RR027303NCRR NIH HHS S10 RR029668NHGRI NIH HHS T32 HG000047NIBIB NIH HHS DP2 EB018658NIGMS NIH HHS K99 GM118909NIGMS NIH HHS R00 GM118909NIGMS NIH HHS R01 GM127463
6 · The paper itself

Abstract

The ability to engineer natural proteins is pivotal to a future, pragmatic biology. CRISPR proteins have revolutionized genome modification, yet the CRISPR-Cas9 scaffold is not ideal for fusions or activation by cellular triggers. Here, we show that a topological rearrangement of Cas9 using circular permutation provides an advanced platform for RNA-guided genome modification and protection. Through systematic interrogation, we find that protein termini can be positioned adjacent to bound DNA, offering a straightforward mechanism for strategically fusing functional domains. Additionally, circular permutation enabled protease-sensing Cas9s (ProCas9s), a unique class of single-molecule effectors possessing programmable inputs and outputs. ProCas9s can sense a wide range of proteases, and we demonstrate that ProCas9 can orchestrate a cellular response to pathogen-associated protease activity. Together, these results provide a toolkit of safer and more efficient genome-modifying enzymes and molecular recorders for the advancement of precision genome engineering in research, agriculture, and biomedicine.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCRISPR-Cas SystemsDNAGene EditingGenomeModels, MolecularRNARNA, Guide, CRISPR-Cas SystemsCRISPR-Associated ProteinsDNARNARNA, Guide, CRISPR-Cas SystemsCas9-CPcircular permutationCRISPR-Casfusion proteinsgenome editingProCas9protein engineering

Identifiers

PMID30633905
PMCPMC6414052

What OpenQuestion holds

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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.