Evidence map›Paper›PMID 40399255›Full record

ArticleNature communications2025

Robust prediction of synthetic gRNA activity and cryptic DNA repair by disentangling cellular CRISPR cleavage outcomes.

Stephan Riesenberg, Philipp Kanis, Rosa Karlic, Tomislav Maricic

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Dual-line Genome-scale CRISPR Screening Enables Robust Target Gene Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Review
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

4 authors.

Stephan RiesenbergDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. stephan_riesenberg@eva.mpg.de.ORCID http://orcid.org/0000-0001-8171-1717
Philipp KanisDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0003-4705-4447
Rosa KarlicBioinformatics Group, Division of Molecular Biology, Department of Biology, University of Zagreb, Zagreb, Croatia.ORCID http://orcid.org/0000-0002-1291-2897
Tomislav MaricicDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0003-3267-0474

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ability to robustly predict guide RNA (gRNA) activity is a long-standing goal for CRISPR applications, as it would reduce the need to pre-screen gRNAs. Quantification of formation of short insertions and deletions (indels) after DNA cleavage by transcribed gRNAs has been typically used to measure and predict gRNA activity. We evaluate the effect of chemically synthesized Cas9 gRNAs on different cellular DNA cleavage outcomes and find that the activity of different gRNAs is largely similar and often underestimated when only indels are scored. We provide a simple linear model that reliably predicts synthetic gRNA activity across cell lines, robustly identifies inefficient gRNAs across different published datasets, and is easily accessible via online genome browser tracks. In addition, we develop a homology-directed repair efficiency prediction tool and show that unintended large-scale repair events are common for Cas9 but not for Cas12a, which may be relevant for safety in gene therapy applications.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDNA RepairRNA, Guide, CRISPR-Cas SystemsBacterial ProteinsCRISPR-Associated Protein 9CRISPR-Associated ProteinsDNA CleavageEndodeoxyribonucleasesGene EditingHEK293 CellsHumansINDEL MutationBacterial ProteinsCas12a proteinCRISPR-Associated Protein 9CRISPR-Associated ProteinsEndodeoxyribonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID40399255
PMCPMC12095496

What OpenQuestion holds

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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.