Evidence map›Paper›PMID 37429857›Full record

ArticleNature communications2023

Cell cycle arrest and p53 prevent ON-target megabase-scale rearrangements induced by CRISPR-Cas9.

G Cullot, J Boutin, S Fayet, F Prat, J Rosier, D Cappellen, I Lamrissi, P Pennamen, J Bouron, S Amintas and 10 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.5field-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

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
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  7. Article
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  9. Article
  10. Article
  11. Article
  12. Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024
    Review
  13. Article
  14. International journal of molecular sciences · 2024
    Article
  15. Article
  16. Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024
    Review
  17. Article
  18. Article
  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

20 authors at 5 institutions in 1 country.

G Cullot *Bordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.ORCID http://orcid.org/0000-0003-3925-705X
J Boutin *Bordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.ORCID http://orcid.org/0000-0001-9948-4129
S Fayet *Bordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
F Prat *Bordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
J RosierBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
D CappellenBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.ORCID http://orcid.org/0000-0002-9634-2595
I LamrissiBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
P PennamenCHU de Bordeaux, department of medical genetics, F-33000, Bordeaux, France.ORCID http://orcid.org/0000-0002-0363-9884
J BouronCHU de Bordeaux, department of medical genetics, F-33000, Bordeaux, France.
S AmintasBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
C ThibaultBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.ORCID http://orcid.org/0000-0002-9420-4180
I MoranvillierBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
E LaharanneCHU de Bordeaux, Tumor Biology and Tumor Bank Laboratory, F-33000, Bordeaux, France.
J P MerlioBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.ORCID http://orcid.org/0000-0002-0305-0850
V Guyonnet-DuperatBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
J M BlouinBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
E RichardBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
S DabernatBordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France.
F Moreau-Gaudry *Bordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France. francois.moreau-gaudry@u-bordeaux.fr.ORCID http://orcid.org/0000-0003-1813-3939
A Bedel *Bordeaux University, INSERM, BRIC, U1312, F-33000, Bordeaux, France. aurelie.bedel@u-bordeaux.fr.
Inserm · FRCentre Hospitalier Universitaire de Bordeaux · FRCentre National de la Recherche Scientifique · FRSciences Po Bordeaux · FRUniversité de Bordeaux · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The CRISPR-Cas9 system has revolutionized our ability to precisely modify the genome and has led to gene editing in clinical applications. Comprehensive analysis of gene editing products at the targeted cut-site has revealed a complex spectrum of outcomes. ON-target genotoxicity is underestimated with standard PCR-based methods and necessitates appropriate and more sensitive detection methods. Here, we present two complementary Fluorescence-Assisted Megabase-scale Rearrangements Detection (FAMReD) systems that enable the detection, quantification, and cell sorting of edited cells with megabase-scale loss of heterozygosity (LOH). These tools reveal rare complex chromosomal rearrangements caused by Cas9-nuclease and show that LOH frequency depends on cell division rate during editing and p53 status. Cell cycle arrest during editing suppresses the occurrence of LOH without compromising editing. These data are confirmed in human stem/progenitor cells, suggesting that clinical trials should consider p53 status and cell proliferation rate during editing to limit this risk by designing safer protocols.

Indexed as

CRISPR-Cas SystemsTumor Suppressor Protein p53Cell Cycle CheckpointsCell DivisionCell SeparationHumansRNARNATumor Suppressor Protein p53

Identifiers

PMID37429857
PMCPMC10333231
OpenAlexW4383815480

What OpenQuestion holds

Textmetadata
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.