Evidence map›Paper›PMID 30850590›Full record

ArticleNature communications2019

CRISPR-Cas9 genome editing induces megabase-scale chromosomal truncations.

Grégoire Cullot, Julian Boutin, Jérôme Toutain, Florence Prat, Perrine Pennamen, Caroline Rooryck, Martin Teichmann, Emilie Rousseau, Isabelle Lamrissi-Garcia, Véronique Guyonnet-Duperat and 10 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 311 papers.

0numbers the graph read from it
0cells of the map it votes in
311citing papers in PubMed
17.8field-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

311 citing papers in PubMed, 466 citations in OpenAlex.

  1. Article
  2. CRISPR/Cas9-based nanodelivery systems for precision gene editing in neuroinflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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  8. Article
  9. Article
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  11. Review
  12. Article
  13. Article
  14. Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  15. Review
  16. Article
  17. Cytosine base editing of LPA in transgenic mice averts large deletions.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  18. Article
  19. Article
  20. Review

251 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

20 authors at 6 institutions in 1 country.

Grégoire CullotUniv. Bordeaux, 33000, Bordeaux, France.
Julian BoutinUniv. Bordeaux, 33000, Bordeaux, France.
Jérôme ToutainMedical genetic laboratory, CHU Bordeaux, 33000, Bordeaux, France.
Florence PratUniv. Bordeaux, 33000, Bordeaux, France.
Perrine PennamenMedical genetic laboratory, CHU Bordeaux, 33000, Bordeaux, France.
Caroline RooryckMedical genetic laboratory, CHU Bordeaux, 33000, Bordeaux, France.
Martin TeichmannUniv. Bordeaux, 33000, Bordeaux, France.
Emilie RousseauUniv. Bordeaux, 33000, Bordeaux, France.
Isabelle Lamrissi-GarciaUniv. Bordeaux, 33000, Bordeaux, France.
Véronique Guyonnet-DuperatINSERM U1035, Biotherapy of genetic diseases, inflammatory disorders and cancers, 33000, Bordeaux, France.
Alice BibeyranINSERM U1035, Biotherapy of genetic diseases, inflammatory disorders and cancers, 33000, Bordeaux, France.
Magalie LalanneUniv. Bordeaux, 33000, Bordeaux, France.
Valérie Prouzet-MauléonUniv. Bordeaux, 33000, Bordeaux, France.
Béatrice TurcqUniv. Bordeaux, 33000, Bordeaux, France.
Cécile GedUniv. Bordeaux, 33000, Bordeaux, France.
Jean-Marc BlouinUniv. Bordeaux, 33000, Bordeaux, France.
Emmanuel RichardUniv. Bordeaux, 33000, Bordeaux, France.
Sandrine DabernatUniv. Bordeaux, 33000, Bordeaux, France.
François Moreau-GaudryUniv. Bordeaux, 33000, Bordeaux, France. francois.moreau-gaudry@u-bordeaux.fr.
Aurélie BedelUniv. Bordeaux, 33000, Bordeaux, France.
Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers · FRInserm · FRUniversité de Bordeaux · FRBordeaux Population Health · FRLaboratoire de Vectorologie et Thérapeutiques Anticancéreuses · FRLaboratory of Excellence GR-Ex · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR-Cas9 is a promising technology for genome editing. Here we use Cas9 nuclease-induced double-strand break DNA (DSB) at the UROS locus to model and correct congenital erythropoietic porphyria. We demonstrate that homology-directed repair is rare compared with NHEJ pathway leading to on-target indels and causing unwanted dysfunctional protein. Moreover, we describe unexpected chromosomal truncations resulting from only one Cas9 nuclease-induced DSB in cell lines and primary cells by a p53-dependent mechanism. Altogether, these side effects may limit the promising perspectives of the CRISPR-Cas9 nuclease system for disease modeling and gene therapy. We show that the single nickase approach could be safer since it prevents on- and off-target indels and chromosomal truncations. These results demonstrate that the single nickase and not the nuclease approach is preferable, not only for modeling disease but also and more importantly for the safe management of future CRISPR-Cas9-mediated gene therapies.

Indexed as

Chromosomes, Human, Pair 10CRISPR-Cas SystemsDNA Breaks, Double-StrandedChromosome DeletionClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9Deoxyribonuclease IDNAFibroblastsGene EditingGenetic TherapyGenome, HumanHEK293 CellsHigh-Throughput Nucleotide SequencingHumansK562 CellsCRISPR-Associated Protein 9Deoxyribonuclease IDNARNA, Guide, CRISPR-Cas SystemsTumor Suppressor Protein p53Uroporphyrinogen III Synthetase

Identifiers

PMID30850590
PMCPMC6408493
OpenAlexW2919006054

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.