Evidence map›Paper›PMID 36064968›Full record

ArticleNature cell biology2022

Massively parallel genomic perturbations with multi-target CRISPR interrogates Cas9 activity and DNA repair at endogenous sites.

Roger S Zou, Alberto Marin-Gonzalez, Yang Liu, Hans B Liu, Leo Shen, Rachel K Dveirin, Jay X J Luo, Reza Kalhor, Taekjip Ha

Open access · hybridAbstract 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 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Genomic repeats for single-cell molecular recording.bioRxiv : the preprint server for biology · 2026
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  7. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
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  13. Review
  14. Article
  15. Article
  16. Biosecurity Primitive: Polymerase X-based Genetic Physical Unclonable Functions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  17. Article
  18. Review
  19. Article
  20. 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

9 authors at 2 institutions in 1 country.

Roger S Zou *Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alberto Marin-Gonzalez *Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yang LiuDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hans B LiuDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Leo ShenDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rachel K DveirinDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jay X J LuoDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Reza KalhorDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Taekjip HaDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. tjha@jhu.edu.ORCID http://orcid.org/0000-0003-2195-6258
Johns Hopkins University · USHoward Hughes Medical Institute · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
BIOMEDICAL ENGINEERING TRAINING PROGRAMT32GM007057 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KANOLD, PATRICK O, KARCHIN, RACHEL · 1985 to 2023
$10.4M
Single Molecule Studies of Nucleic Acids RemodelingR35GM122569 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Taekjip Ha · 2017 to 2026
$3.5M
Chromatin Function During Transcription and DNA Repair at Single Molecule Resolutionin Living CellsU01DK127432 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HA, TAEKJIP, JOHNSON, MARGARET ELLEN · 2020 to 2024
$3.5M
Dynamics of lineage-specific genome reorganization in gastrulation and their response to disease-associated epigenetic perturbationsU01HL156056 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KALHOR, REZA · 2020 to 2024
$3.1M
High-throughput characterization of epigenetic context on DNA double strand break repair dynamicsF30CA254160 · NCI · JOHNS HOPKINS UNIVERSITY · PI ZOU, ROGER · 2020 to 2022
$151k
Howard Hughes Medical InstituteNCI NIH HHS F30 CA254160NHLBI NIH HHS U01 HL156056NIDDK NIH HHS U01 DK127432NIGMS NIH HHS R35 GM122569NIGMS NIH HHS T32 GM007057NIGMS NIH HHS T32 GM007445NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

Here we present an approach that combines a clustered regularly interspaced short palindromic repeats (CRISPR) system that simultaneously targets hundreds of epigenetically diverse endogenous genomic sites with high-throughput sequencing to measure Cas9 dynamics and cellular responses at scale. This massive multiplexing of CRISPR is enabled by means of multi-target guide RNAs (mgRNAs), degenerate guide RNAs that direct Cas9 to a pre-determined number of well-mapped sites. mgRNAs uncovered generalizable insights into Cas9 binding and cleavage, revealing rapid post-cleavage Cas9 departure and repair factor loading at protospacer adjacent motif-proximal genomic DNA. Moreover, by bypassing confounding effects from guide RNA sequence, mgRNAs unveiled that Cas9 binding is enhanced at chromatin-accessible regions, and cleavage by bound Cas9 is more efficient near transcribed regions. Combined with light-mediated activation and deactivation of Cas9 activity, mgRNAs further enabled high-throughput study of the cellular response to double-strand breaks with high temporal resolution, revealing the presence, extent (under 2 kb) and kinetics (~1 h) of reversible DNA damage-induced chromatin decompaction. Altogether, this work establishes mgRNAs as a generalizable platform for multiplexing CRISPR and advances our understanding of intracellular Cas9 activity and the DNA damage response at endogenous loci.

Indexed as

CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas SystemsChromatinDNADNA RepairGenomicsChromatinDNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID36064968
PMCPMC9481459
OpenAlexW4294636858

What OpenQuestion holds

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LicenceCC BY
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.