Evidence map›Paper›PMID 30936531›Full record

ArticleNature structural & molecular biology2019

Broad-spectrum enzymatic inhibition of CRISPR-Cas12a.

Gavin J Knott, Brittney W Thornton, Marco J Lobba, Jun-Jie Liu, Basem Al-Shayeb, Kyle E Watters, Jennifer A Doudna

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing 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

65 citing papers in PubMed.

  1. Article
  2. Article
  3. AcrVA3 Is a Double Strand DNA-Cleaving Anti-CRISPR That Indirectly Inhibits Cas12.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Protective antigen-mediated delivery of an anti-CRISPR protein for precision genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. CRISPR-Cas applications in agriculture and plant research.Nature reviews. Molecular cell biology · 2025
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

5 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

7 authors.

Gavin J KnottDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-9007-6273
Brittney W ThorntonDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Marco J LobbaDepartment of Chemistry, University of California, Berkeley, CA, USA.
Jun-Jie LiuDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Basem Al-ShayebDepartment of Plant and Microbial Biology, University of California, Berkeley, CA, USA.
Kyle E WattersDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-6858-6632
Jennifer A DoudnaDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA. doudna@berkeley.edu.ORCID http://orcid.org/0000-0001-9161-999X

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Cas12a is a bacterial RNA-guided nuclease used widely for genome editing and, more recently, as a molecular diagnostic. In bacteria, Cas12a enzymes can be inhibited by bacteriophage-derived proteins, anti-CRISPRs (Acrs), to thwart clustered regularly interspaced short palindromic repeat (CRISPR) adaptive immune systems. How these inhibitors disable Cas12a by preventing programmed DNA cleavage is unknown. We show that three such inhibitors (AcrVA1, AcrVA4 and AcrVA5) block Cas12a activity via functionally distinct mechanisms, including a previously unobserved enzymatic strategy. AcrVA4 and AcrVA5 inhibit recognition of double-stranded DNA (dsDNA), with AcrVA4 driving dimerization of Cas12a. In contrast, AcrVA1 is a multiple-turnover inhibitor that triggers cleavage of the target-recognition sequence of the Cas12a-bound guide RNA to irreversibly inactivate the Cas12a complex. These distinct mechanisms equip bacteriophages with tools to evade CRISPR-Cas12a and support biotechnological applications for which multiple-turnover enzymatic inhibition of Cas12a is desirable.

Indexed as

Adaptive ImmunityCRISPR-Cas SystemsDNA CleavageEndoribonucleasesGene EditingProtein MultimerizationEndoribonucleases

Identifiers

PMID30936531
PMCPMC6449189

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.