Evidence map›Paper›PMID 41588195›Full record

ArticleNature chemical biology2026

De novo design of potent CRISPR-Cas13 inhibitors.

Cyntia Taveneau, Her Xiang Chai, Jovita D'Silva, Rebecca S Bamert, Honglin Chen, Brooke K Hayes, Roland W Calvert, Jacob Purcell, Daniel J Curwen, Fabian Munder and 6 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
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.

Cyntia TaveneauDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. cyntia.taveneau@monash.edu.ORCID http://orcid.org/0000-0002-3395-4957
Her Xiang ChaiDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0009-0007-0116-257X
Jovita D'SilvaDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0009-0004-9468-4729
Rebecca S BamertDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0000-0001-7685-713X
Honglin ChenPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Brooke K HayesDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0000-0002-6942-785X
Roland W CalvertDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Jacob PurcellDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0009-0003-9157-6928
Daniel J CurwenSchool of Chemistry, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0009-0004-2258-5983
Fabian MunderDepartment of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0009-0005-5327-3138
Lisandra L MartinSchool of Chemistry, Monash University, Clayton, Victoria, Australia.
Jeremy J BarrSchool of Biological Sciences, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0000-0001-5603-5294
Joseph RosenbluhDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.ORCID http://orcid.org/0000-0001-9815-8049
Mohamed FarehPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Rhys GrinterAI Protein Design Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. rhys.grinter@unimelb.edu.au.ORCID http://orcid.org/0000-0002-8195-5348
Gavin J KnottDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. gavin.knott@monash.edu.ORCID http://orcid.org/0000-0002-9007-6273

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR-Cas systems are transformative tools for gene editing that can be tuned or controlled by anti-CRISPRs (Acrs)-phage-derived inhibitors that regulate CRISPR-Cas activity. However, Acrs that can inhibit biotechnologically relevant CRISPR systems are relatively rare and challenging to discover. To overcome this limitation, we describe a highly successful and rapid approach that leverages de novo protein design to develop new-to-nature proteins for controlling CRISPR-Cas activity. Here, using Leptotrichia buccalis CRISPR-Cas13a as a representative example, we demonstrate that Acrs designed using artificial intelligence (AIcrs) are capable of highly potent and specific inhibition of CRISPR-Cas13a nuclease activity. We present a comprehensive workflow for design validation and demonstrate AIcr functionality in controlling CRISPR-Cas13 activity in bacterial and human cells. The ability to design bespoke inhibitors of Cas effectors will contribute to the ongoing development of CRISPR-Cas tools in diverse applications across research, medicine, agriculture and microbiology.

Indexed as

CRISPR-Cas SystemsDrug DesignHumansLeptotrichia

Identifiers

PMID41588195
PMCPMC13423800

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.