Evidence map›Paper›PMID 39604565›Full record

ArticleNature biotechnology2025

Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.

Grégoire Cullot, Eric J Aird, Moritz F Schlapansky, Charles D Yeh, Lilly van de Venn, Iryna Vykhlyantseva, Susanne Kreutzer, Dominic Mailänder, Bohdan Lewków, Julia Klermund and 7 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
–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

55 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Pooled it
  2. Review
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  4. Article
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  7. 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
    Article
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  9. Article
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  15. Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Grégoire CullotDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland. gregoire.cullot@biol.ethz.ch.ORCID http://orcid.org/0000-0003-3925-705X
Eric J AirdDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-4873-042X
Moritz F SchlapanskyDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-6072-7840
Charles D YehDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-2707-6035
Lilly van de VennDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-0158-1225
Iryna VykhlyantsevaDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Susanne KreutzerDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Dominic MailänderDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Bohdan LewkówDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Julia KlermundInstitute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-6069-8189
Christian MontelleseCSL Behring Research, Bern, Switzerland.ORCID http://orcid.org/0009-0009-4261-088X
Martina BiserniCSL Behring Research, Bern, Switzerland.
Florian AeschimannCSL Behring Research, Bern, Switzerland.ORCID http://orcid.org/0000-0001-5213-034X
Cédric VonarburgCSL Behring Research, Bern, Switzerland.
Helmuth GehartDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-9165-5824
Toni CathomenInstitute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-7757-4630
Jacob E CornDepartment of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland. jacob.corn@biol.ethz.ch.ORCID http://orcid.org/0000-0002-7798-5309

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) DFG CA 311/4-1EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 855741-DDREAMM-ERC-2019-SyG
6 · The paper itself

Abstract

The DNA-PKcs inhibitor AZD7648 enhances CRISPR-Cas9-directed homology-directed repair efficiencies, with potential for clinical utility, but its possible on-target consequences are unknown. We found that genome editing with AZD7648 causes frequent kilobase-scale and megabase-scale deletions, chromosome arm loss and translocations. These large-scale chromosomal alterations evade detection through typical genome editing assays, prompting caution in deploying AZD7648 and reinforcing the need to investigate multiple types of potential editing outcomes.

Indexed as

DNA-Activated Protein KinaseGene EditingPyrazolesRecombinational DNA RepairCRISPR-Cas SystemsHumansProtein Kinase InhibitorsPyrimidinesDNA-Activated Protein KinaselarotrectinibProtein Kinase InhibitorsPyrazolesPyrimidines

Identifiers

PMID39604565
PMCPMC12611759

What OpenQuestion holds

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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.