Evidence map›Paper›PMID 32284602›Full record

ArticleNature chemical biology2020

Computational design of anti-CRISPR proteins with improved inhibition potency.

Jan Mathony, Zander Harteveld, Carolin Schmelas, Julius Upmeier Zu Belzen, Sabine Aschenbrenner, Wei Sun, Mareike D Hoffmann, Christina Stengl, Andreas Scheck, Sandrine Georgeon and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
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  3. Article
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  5. Article
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Atomic-scale insights into allosteric inhibition and evolutional rescue mechanism ofComputational and structural biotechnology journal · 2021
    Article
  14. Base editing: advances and therapeutic opportunities.Nature reviews. Drug discovery · 2020
    Review
  15. Article
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

16 authors.

Jan Mathony *Synthetic Biology Group, BioQuant Center, University of Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-4081-9953
Zander Harteveld *Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Carolin Schmelas *Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-8859-7168
Julius Upmeier Zu BelzenSynthetic Biology Group, BioQuant Center, University of Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0966-4458
Sabine AschenbrennerSynthetic Biology Group, BioQuant Center, University of Heidelberg, Heidelberg, Germany.
Wei SunNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Mareike D HoffmannSynthetic Biology Group, BioQuant Center, University of Heidelberg, Heidelberg, Germany.
Christina StenglSynthetic Biology Group, BioQuant Center, University of Heidelberg, Heidelberg, Germany.
Andreas ScheckInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Sandrine GeorgeonInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Stéphane RossetInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Yanli WangNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Dirk GrimmDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-6227-5665
Roland EilsDigital Health Center, Berlin Institute of Health (BIH) and Charité, Berlin, Germany.
Bruno E CorreiaInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. bruno.correia@epfl.ch.ORCID http://orcid.org/0000-0002-7377-8636
Dominik NiopekSynthetic Biology Group, BioQuant Center, University of Heidelberg, Heidelberg, Germany. dominik.niopek@bioquant.uni-heidelberg.de.ORCID http://orcid.org/0000-0001-7479-530X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anti-CRISPR (Acr) proteins are powerful tools to control CRISPR-Cas technologies. However, the available Acr repertoire is limited to naturally occurring variants. Here, we applied structure-based design on AcrIIC1, a broad-spectrum CRISPR-Cas9 inhibitor, to improve its efficacy on different targets. We first show that inserting exogenous protein domains into a selected AcrIIC1 surface site dramatically enhances inhibition of Neisseria meningitidis (Nme)Cas9. Then, applying structure-guided design to the Cas9-binding surface, we converted AcrIIC1 into AcrIIC1X, a potent inhibitor of the Staphylococcus aureus (Sau)Cas9, an orthologue widely applied for in vivo genome editing. Finally, to demonstrate the utility of AcrIIC1X for genome engineering applications, we implemented a hepatocyte-specific SauCas9 ON-switch by placing AcrIIC1X expression under regulation of microRNA-122. Our work introduces designer Acrs as important biotechnological tools and provides an innovative strategy to safeguard CRISPR technologies.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsAmino Acid SequenceCell Line, TumorCRISPR-Associated Protein 9Gene EditingGenome, HumanHEK293 CellsHepatocytesHumansMicroRNAsModels, MolecularMutagenesis, InsertionalNeisseria meningitidisPlasmidsProtein DomainsCRISPR-Associated Protein 9MicroRNAsMIRN122 microRNA, humanRNA, Guide, CRISPR-Cas Systems

Identifiers

What OpenQuestion holds

Textmetadata
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.