Evidence map›Paper›PMID 30010673›Full record

ArticleNature biotechnology2018

Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements.

Michael Kosicki, Kärt Tomberg, Allan Bradley

Open access · greenAbstract readLetter
In one paragraph

Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,159 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,159citing papers in PubMed, 1 pooled it
87.0field-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

1,159 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,828 citations in OpenAlex.

  1. CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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  15. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  17. The landscape and trajectory of global CRISPR therapeutics.Molecular therapy. Nucleic acids · 2026
    Review
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1,099 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Michael KosickiWellcome Sanger Institute, Hinxton, UK.
Kärt TombergWellcome Sanger Institute, Hinxton, UK.
Allan BradleyWellcome Sanger Institute, Hinxton, UK.
Wellcome Sanger Institute · GB

Funding

Wellcome Trust 079643
6 · The paper itself

Abstract

CRISPR-Cas9 is poised to become the gene editing tool of choice in clinical contexts. Thus far, exploration of Cas9-induced genetic alterations has been limited to the immediate vicinity of the target site and distal off-target sequences, leading to the conclusion that CRISPR-Cas9 was reasonably specific. Here we report significant on-target mutagenesis, such as large deletions and more complex genomic rearrangements at the targeted sites in mouse embryonic stem cells, mouse hematopoietic progenitors and a human differentiated cell line. Using long-read sequencing and long-range PCR genotyping, we show that DNA breaks introduced by single-guide RNA/Cas9 frequently resolved into deletions extending over many kilobases. Furthermore, lesions distal to the cut site and crossover events were identified. The observed genomic damage in mitotically active cells caused by CRISPR-Cas9 editing may have pathogenic consequences.

Indexed as

CRISPR-Cas SystemsDNA Breaks, Double-StrandedSequence DeletionAnimalsGenotypeHumansMiceMutagenesisPolymerase Chain Reaction

Identifiers

PMID30010673
PMCPMC6390938
OpenAlexW2883697525

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.