Evidence map›Paper›PMID 37400536›Full record

ArticleNature chemical biology2023

An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity.

Tong Wu, Chang Liu, Siyuan Zou, Ruitu Lyu, Bowei Yang, Hao Yan, Minglei Zhao, Weixin Tang

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2023. 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 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
12.2field-weighted citation impact, top 1% 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

56 citing papers in PubMed, 79 citations in OpenAlex.

  1. Base Editing: Mechanisms and Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2027
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Tong Wu *Department of Chemistry, The University of Chicago, Chicago, IL, USA.ORCID 0000-0001-9968-9909
Chang Liu *Department of Chemistry, The University of Chicago, Chicago, IL, USA.
Siyuan Zou *Department of Chemistry, The University of Chicago, Chicago, IL, USA.ORCID 0009-0005-7771-3644
Ruitu LyuDepartment of Chemistry, The University of Chicago, Chicago, IL, USA.
Bowei YangInstitute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
Hao YanDepartment of Chemistry, The University of Chicago, Chicago, IL, USA.
Minglei ZhaoInstitute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA. mlzhao@uchicago.edu.ORCID 0000-0001-5832-6060
Weixin TangDepartment of Chemistry, The University of Chicago, Chicago, IL, USA. weixintang@uchicago.edu.ORCID 0000-0002-5739-5416
University of Chicago · USUniversity of Illinois Chicago · US

Funding

Structural and Functional Studies of Molecular Machines Involved in Chemical Modifications of MacromoleculesR35GM143052 · NIGMS · UNIVERSITY OF CHICAGO · PI ZHAO, MINGLEI · 2021 to 2025
$2.1M
Beagle-3: A Shared GPU Cluster for Biomolecular SciencesS10OD028655 · OD · UNIVERSITY OF CHICAGO · PI ROUX, BENOIT · 2020 to 2020
$2.0M
NIGMS NIH HHS R35 GM143052NIH HHS S10 OD028655
6 · The paper itself

Abstract

Compact CRISPR-Cas systems offer versatile treatment options for genetic disorders, but their application is often limited by modest gene-editing activity. Here we present enAsCas12f, an engineered RNA-guided DNA endonuclease up to 11.3-fold more potent than its parent protein, AsCas12f, and one-third of the size of SpCas9. enAsCas12f shows higher DNA cleavage activity than wild-type AsCas12f in vitro and functions broadly in human cells, delivering up to 69.8% insertions and deletions at user-specified genomic loci. Minimal off-target editing is observed with enAsCas12f, suggesting that boosted on-target activity does not impair genome-wide specificity. We determine the cryo-electron microscopy (cryo-EM) structure of the AsCas12f-sgRNA-DNA complex at a resolution of 2.9 Å, which reveals dimerization-mediated substrate recognition and cleavage. Structure-guided single guide RNA (sgRNA) engineering leads to sgRNA-v2, which is 33% shorter than the full-length sgRNA, but with on par activity. Together, the engineered hypercompact AsCas12f system enables robust and faithful gene editing in mammalian cells.

Indexed as

Gene EditingRNA, Guide, CRISPR-Cas SystemsAnimalsCRISPR-Cas SystemsCryoelectron MicroscopyDNAHumansMammalsDNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37400536
PMCPMC10625714
OpenAlexW4382989293

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.