Evidence map›Paper›PMID 39698811›Full record

ArticleNucleic acids research2025

CRISPR-Cas12a bends DNA to destabilize base pairs during target interrogation.

Katarzyna M Soczek, Joshua C Cofsky, Owen T Tuck, Honglue Shi, Jennifer A Doudna

Erratum issuedAbstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Architecture of a DNA-guided Cas12a.Nature structural & molecular biology · 2026
    Article
  2. Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026
    Review
  3. Rho (bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Structure and evolution-guided design of minimal RNA-guided nucleases.bioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Katarzyna M SoczekDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
Joshua C CofskyDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
Owen T TuckInnovative Genomics Institute; University of California, Berkeley, CA, USA.
Honglue ShiDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.ORCID 0000-0003-3847-1652
Jennifer A DoudnaDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.ORCID 0000-0001-9161-999X

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$103.4M
Project 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$35.7M
RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2018 to 2026
$21.4M
Resource Core II: In Vivo CoreU19NS132303 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI FYODOR D URNOV · 2023 to 2026
$19.7M
Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systemsU01AI142817 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BANFIELD, JILLIAN, DOUDNA, JENNIFER A · 2018 to 2022
$2.0M
Cas9 RNP delivery to immune cells in vivo via molecular targetingUH3AI150552 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI DOUDNA, JENNIFER A, WILSON, ROSS C · 2022 to 2022
$1.3M
Targeted Delivery of Cas9 to Lung Epithelial Cells using Enveloped Delivery VehiclesR21HL173710 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI DOUDNA, JENNIFER A · 2024 to 2025
$520k
Apple Tree Partners 24 180Department of Energy DE-AC02-05CH11231Helen Hay Whitney FoundationHHMI Fellow of The Jane Coffin Childs Fund for Medical ResearchHoward Hughes Medical InstituteInnovative Genomics InstituteKoret-Berkeley-TAULawrence Livermore National LaboratoryMr. Li Ka ShingNational Science Foundation 2334028National Science Foundation Graduate Research FellowshipNHLBI NIH HHS R21 HL173710NHLBI NIH HHS R21HL173710NIAID NIH HHS U01 AI142817NIAID NIH HHS U19 AI135990NIAID NIH HHS U19 AI171110NIAID NIH HHS U54 AI170792NIAID NIH HHS UH3 AI150552NIH HHS U19AI171110NINDS NIH HHS U19 NS132303NINDS NIH HHS U19NS132303Panattoni Family FoundationUCB-Hampton University Summer Program
6 · The paper itself

Abstract

RNA-guided endonucleases are involved in processes ranging from adaptive immunity to site-specific transposition and have revolutionized genome editing. CRISPR-Cas9, -Cas12 and related proteins use guide RNAs to recognize ∼20-nucleotide target sites within genomic DNA by mechanisms that are not yet fully understood. We used structural and biochemical methods to assess early steps in DNA recognition by Cas12a protein-guide RNA complexes. We show here that Cas12a initiates DNA target recognition by bending DNA to induce transient nucleotide flipping that exposes nucleobases for DNA-RNA hybridization. Cryo-EM structural analysis of a trapped Cas12a-RNA-DNA surveillance complex and fluorescence-based conformational probing show that Cas12a-induced DNA helix destabilization enables target discovery and engagement. This mechanism of initial DNA interrogation resembles that of CRISPR-Cas9 despite distinct evolutionary origins and different RNA-DNA hybridization directionality of these enzyme families. Our findings support a model in which RNA-mediated DNA interference begins with local helix distortion by transient CRISPR-Cas protein binding.

Indexed as

Bacterial ProteinsCRISPR-Associated ProteinsCRISPR-Cas SystemsDNAEndodeoxyribonucleasesBase PairingCryoelectron MicroscopyGene EditingModels, MolecularNucleic Acid ConformationRNA, Guide, CRISPR-Cas SystemsBacterial ProteinsCas12a proteinCRISPR-Associated ProteinsDNAEndodeoxyribonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39698811
PMCPMC11754666

What OpenQuestion holds

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Registered trials

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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.