Evidence map›Paper›PMID 32732424›Full record

ArticleScience (New York, N.Y.)2020

DNA capture by a CRISPR-Cas9-guided adenine base editor.

Audrone Lapinaite, Gavin J Knott, Cody M Palumbo, Enrique Lin-Shiao, Michelle F Richter, Kevin T Zhao, Peter A Beal, David R Liu, Jennifer A Doudna

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
9.4field-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

129 citing papers in PubMed, 201 citations in OpenAlex.

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69 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

9 authors at 5 institutions in 1 country.

Audrone Lapinaite *Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.ORCID 0000-0002-9427-9342
Gavin J Knott *Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.ORCID 0000-0002-9007-6273
Cody M PalumboDepartment of Chemistry, University of California, Davis, CA 95616, USA.ORCID 0000-0002-2083-0517
Enrique Lin-ShiaoDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.ORCID 0000-0001-5396-9614
Michelle F RichterMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA.ORCID 0000-0002-6113-6820
Kevin T ZhaoMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA.ORCID 0000-0003-3440-2094
Peter A BealDepartment of Chemistry, University of California, Davis, CA 95616, USA.ORCID 0000-0003-4855-7185
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA.ORCID 0000-0002-9943-7557
Jennifer A DoudnaDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. doudna@berkeley.edu.ORCID 0000-0001-9161-999X
Broad Institute · USUniversity of California, Berkeley · USUniversity of California, Davis · USDiscovery Institute · USGladstone Institutes · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
The Bioorganic Chemistry Of RNA Editing By ADARSR01GM061115 · NIGMS · UNIVERSITY OF UTAH · PI BEAL, PETER A. · 2001 to 2020
$4.5M
Principles of Scientific Citizenship: Ethics, Communication, and Leadership for ScientistsT32GM095450 · NIGMS · HARVARD UNIVERSITY · PI WALKER, SUZANNE · 2011 to 2020
$3.5M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
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
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB022376 · NIBIB · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2019
$1.8M
UC Davis Training Program in Chemical BiologyT32GM113770 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BEAL, PETER A. · 2015 to 2019
$742k
High Definition Ion Mobility SpectrometerS10OD020062 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI WILLIAMS, EVAN R · 2015 to 2015
$590k
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIAID NIH HHS U01 AI142817NIBIB NIH HHS R01 EB022376NIGMS NIH HHS R01 GM061115NIGMS NIH HHS R35 GM118062NIGMS NIH HHS T32 GM095450NIGMS NIH HHS T32 GM113770NIH HHS S10 OD020062
6 · The paper itself

Abstract

CRISPR-Cas-guided base editors convert A•T to G•C, or C•G to T•A, in cellular DNA for precision genome editing. To understand the molecular basis for DNA adenosine deamination by adenine base editors (ABEs), we determined a 3.2-angstrom resolution cryo-electron microscopy structure of ABE8e in a substrate-bound state in which the deaminase domain engages DNA exposed within the CRISPR-Cas9 R-loop complex. Kinetic and structural data suggest that ABE8e catalyzes DNA deamination up to ~1100-fold faster than earlier ABEs because of mutations that stabilize DNA substrates in a constrained, transfer RNA-like conformation. Furthermore, ABE8e's accelerated DNA deamination suggests a previously unobserved transient DNA melting that may occur during double-stranded DNA surveillance by CRISPR-Cas9. These results explain ABE8e-mediated base-editing outcomes and inform the future design of base editors.

Indexed as

CRISPR-Cas SystemsGene EditingAdenineAdenosine DeaminaseCRISPR-Associated Protein 9Cryoelectron MicroscopyDeaminationDNAEscherichia coli ProteinsAdenineAdenosine DeaminaseCRISPR-Associated Protein 9DNAEscherichia coli ProteinsTadA protein, E coli

Identifiers

PMID32732424
PMCPMC8598131
OpenAlexW3046580469

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.