Evidence map›Paper›PMID 39592573›Full record

ArticleNature communications2024

The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations.

Ananth Pallaseni, Elin Madli Peets, Gareth Girling, Luca Crepaldi, Ivan Kuzmin, Marilin Moor, Núria Muñoz-Subirana, Joost Schimmel, Özdemirhan Serçin, Balca R Mardin and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Article
  2. In vivo systematic detection of the outcomes of CRISPR-Cas9-mediated DNA repair in skeletal muscle stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Ananth Pallaseni *Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.ORCID 0000-0002-4840-195X
Elin Madli Peets *Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.ORCID 0000-0002-3479-1969
Gareth GirlingWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Luca CrepaldiWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Ivan KuzminDepartment of Computer Science, University of Tartu, Tartu, Estonia.
Marilin MoorDepartment of Computer Science, University of Tartu, Tartu, Estonia.
Núria Muñoz-SubiranaDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Joost SchimmelDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Özdemirhan SerçinBioMed X Institute (GmbH), Heidelberg, Germany.
Balca R MardinBioMed X Institute (GmbH), Heidelberg, Germany.
Marcel TijstermanDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0001-8465-9002
Hedi PetersonDepartment of Computer Science, University of Tartu, Tartu, Estonia.
Michael KosickiDepartment of Medicine, University of Cambridge, Cambridge, UK. mkosicki@lbl.gov.
Leopold PartsWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. leopold.parts@sanger.ac.uk.ORCID 0000-0002-2618-670X

Funding

Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetR01HG003988 · NHGRI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Len Alexander Pennacchio · 2006 to 2026
$24.1M
NHGRI NIH HHS R01 HG003988Wellcome TrustWellcome Trust (Wellcome) 220540/Z/20/A
6 · The paper itself

Abstract

Repair of double-stranded breaks generated by CRISPR/Cas9 is highly dependent on the flanking DNA sequence. To learn about interactions between DNA repair and target sequence, we measure frequencies of over 236,000 distinct Cas9-generated mutational outcomes at over 2800 synthetic target sequences in 18 DNA repair deficient mouse embryonic stem cells lines. We classify the outcomes in an unbiased way, finding a specialised role for Prkdc (DNA-PKcs protein) and Polm in creating 1 bp insertions matching the nucleotide on the protospacer-adjacent motif side of the break, a variable involvement of Nbn and Polq in the creation of different deletion outcomes, and uni-directional deletions dependent on both end-protection and end-resection. Using our dataset, we build predictive models of the mutagenic outcomes of Cas9 scission that outperform the current standards. This work improves our understanding of DNA repair gene function, and provides avenues for more precise modulation of Cas9-generated mutations.

Indexed as

CRISPR-Cas SystemsDNA-Activated Protein KinaseDNA RepairMutationAnimalsCell LineCRISPR-Associated Protein 9DNA-Binding ProteinsDNA Breaks, Double-StrandedDNA-Directed DNA PolymeraseGene EditingMiceMouse Embryonic Stem CellsNuclear ProteinsCRISPR-Associated Protein 9DNA-Activated Protein KinaseDNA-Binding ProteinsDNA-Directed DNA PolymeraseNuclear ProteinsPrkdc protein, mouse

Identifiers

PMID39592573
PMCPMC11599590

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Registered trials

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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.