Evidence map›Paper›PMID 36879061›Full record

ArticleNature chemical biology2023

A chemically controlled Cas9 switch enables temporal modulation of diverse effectors.

Cindy T Wei, Nicholas A Popp, Omri Peleg, Rachel L Powell, Elhanan Borenstein, Dustin J Maly, Douglas M Fowler

Open 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. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 18 citations in OpenAlex.

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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

7 authors at 4 institutions in 3 countries.

Cindy T WeiMolecular and Cellular Biology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-0032-9581
Nicholas A PoppDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0001-9374-3070
Omri PelegThe Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
Rachel L PowellDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Elhanan BorensteinThe Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.ORCID 0000-0003-3002-0945
Dustin J MalyDepartment of Chemistry, University of Washington, Seattle, WA, USA. djmaly@uw.edu.ORCID 0000-0003-0094-0177
Douglas M FowlerDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. dfowler@uw.edu.ORCID 0000-0001-7614-1713
University of Washington · USGenomics Institute of the Novartis Research Foundation · USSanta Fe Institute · USTel Aviv University · IL

Funding

Technology to understand genetic variant effects in contextRM1HG010461 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Bruce Colston Trapnell · 2019 to 2026
$18.9M
Large-Scale Methods for Assessing the Consequences of Mutations in ProteinsR01GM109110 · NIGMS · UNIVERSITY OF WASHINGTON · PI FOWLER, DOUGLAS M · 2014 to 2021
$2.4M
Chemical Genetic Analysis of RAS SignalingR01GM145011 · NIGMS · UNIVERSITY OF WASHINGTON · PI MALY, DUSTIN J · 2022 to 2025
$1.5M
Comprehensive Characterization of Missense Variants in Factor IXF30HL151075 · NHLBI · UNIVERSITY OF WASHINGTON · PI POPP, NICHOLAS ANTHONY · 2020 to 2023
$178k
NHGRI NIH HHS RM1 HG010461NHLBI NIH HHS F30 HL151075NIGMS NIH HHS R01 GM109110NIGMS NIH HHS R01 GM145011
6 · The paper itself

Abstract

CRISPR-Cas9 has yielded a plethora of effectors, including targeted transcriptional activators, base editors and prime editors. Current approaches for inducibly modulating Cas9 activity lack temporal precision and require extensive screening and optimization. We describe a versatile, chemically controlled and rapidly activated single-component DNA-binding Cas9 switch, ciCas9, which we use to confer temporal control over seven Cas9 effectors, including two cytidine base editors, two adenine base editors, a dual base editor, a prime editor and a transcriptional activator. Using these temporally controlled effectors, we analyze base editing kinetics, showing that editing occurs within hours and that rapid early editing of nucleotides predicts eventual editing magnitude. We also reveal that editing at preferred nucleotides within target sites increases the frequency of bystander edits. Thus, the ciCas9 switch offers a simple, versatile approach to generating chemically controlled Cas9 effectors, informing future effector engineering and enabling precise temporal effector control for kinetic studies.

Indexed as

CRISPR-Cas SystemsGene EditingAdenineKineticsNucleotidesAdenineNucleotides

Identifiers

PMID36879061
PMCPMC10480357
OpenAlexW4323310009

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.