Evidence map›Paper›PMID 36396978›Full record

ArticleNature cell biology2022

A general approach to identify cell-permeable and synthetic anti-CRISPR small molecules.

Donghyun Lim, Qingxuan Zhou, Kurt J Cox, Benjamin K Law, Miseon Lee, Praveen Kokkonda, Vedagopuram Sreekanth, Rajaiah Pergu, Santosh K Chaudhary, Soumyashree A Gangopadhyay and 12 more

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. 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
  8. Article
  9. 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

22 authors at 3 institutions in 2 countries.

Donghyun Lim *Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Qingxuan Zhou *Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-8303-8666
Kurt J Cox *Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Benjamin K Law *Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Miseon Lee *Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-9394-2643
Praveen Kokkonda *Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Vedagopuram Sreekanth *Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Rajaiah PerguChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Santosh K ChaudharyChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Soumyashree A GangopadhyayChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Basudeb MajiChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sophia LaiChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yuka AmakoDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
David B ThompsonDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Hari K K SubramanianDepartment of Mechanical Engineering, University of California-Riverside, Riverside, CA, USA.ORCID 0000-0003-2956-9279
Michael F MeslehCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Vlado DančíkChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Paul A ClemonsChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-1800-5112
Bridget K WagnerChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-2629-361X
Christina M WooDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID 0000-0001-8687-9105
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3535-2076
Amit ChoudharyChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, USA. achoudhary@bwh.harvard.edu.ORCID 0000-0002-8437-0150
Broad Institute · USHarvard University · USUniversity of California, Riverside · US

Funding

Chemical approaches for precision genome editingR01GM137606 · NIGMS · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT · 2021 to 2024
$1.5M
Development of synthetic gene drives using small moleculesR01GM132825 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI AKBARI, OMAR SULTAN, CHOUDHARY, AMIT · 2019 to 2022
$1.4M
Opera Phenix high-throughput microplate confocal imager for high-content screeningS10OD026839 · OD · BROAD INSTITUTE, INC. · PI WAGNER, BRIDGET K · 2019 to 2019
$1.0M
NIGMS NIH HHS R01 GM132825NIGMS NIH HHS R01 GM137606NIH HHS S10 OD026839
6 · The paper itself

Abstract

The need to control the activity and fidelity of CRISPR-associated nucleases has resulted in a demand for inhibitory anti-CRISPR molecules. The small-molecule inhibitor discovery platforms available at present are not generalizable to multiple nuclease classes, only target the initial step in the catalytic activity and require high concentrations of nuclease, resulting in inhibitors with suboptimal attributes, including poor potency. Here we report a high-throughput discovery pipeline consisting of a fluorescence resonance energy transfer-based assay that is generalizable to contemporary and emerging nucleases, operates at low nuclease concentrations and targets all catalytic steps. We applied this pipeline to identify BRD7586, a cell-permeable small-molecule inhibitor of SpCas9 that is twofold more potent than other inhibitors identified to date. Furthermore, unlike the reported inhibitors, BRD7586 enhanced SpCas9 specificity and its activity was independent of the genomic loci, DNA-repair pathway or mode of nuclease delivery. Overall, these studies describe a general pipeline to identify inhibitors of contemporary and emerging CRISPR-associated nucleases.

Indexed as

Genomics

Identifiers

PMID36396978
PMCPMC9891305
OpenAlexW4309219010

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.