Evidence map›Paper›PMID 41184307›Full record

ArticleNature communications2025

Unveiling the cut-and-repair cycle of designer nucleases in human stem and T cells via CLEAR-time dPCR.

Nathan White, John Alexander Chalk, Yi-Ting Hu, Samuel Mark Pins, Chinnu Rose Joseph, Panagiotis Antoniou, Sandra Wimberger, Stina Svensson, Soraia Patricia Caetano-Silva, Anne Charlotte Adriane Mudde and 13 more

Abstract read
PubMed Full text at PMC Publisher
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. 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

23 authors.

Nathan WhiteInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-1109-5100
John Alexander ChalkInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Yi-Ting HuInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Samuel Mark PinsInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Chinnu Rose JosephGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Gothenburg, Sweden.
Panagiotis AntoniouGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Gothenburg, Sweden.
Sandra WimbergerGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-0541-7780
Stina SvenssonInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Soraia Patricia Caetano-SilvaInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Anne Charlotte Adriane MuddeInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Rajeev RaiInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Sridhar SelvarajDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
William Nelson FeistDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5870-4460
Marianna RomitoInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Grzegorz SienskiGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-2730-7710
Roberto NitschCell and Gene therapy Safety, Clinical Pharmacology and Safety Sciences R&D, AstraZeneca, Gothenburg, Sweden.ORCID http://orcid.org/0000-0001-8766-6267
Claire BoothInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-2626-5037
Giorgia SantilliInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0003-1776-1984
Alessia CavazzaInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-4735-2121
Matthew Hebden PorteusDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3850-4648
Marcello MarescaGenome Engineering, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-0796-661X
Adrian James ThrasherInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-6097-6115
Giandomenico TurchianoInfection, Immunity, and Inflammation Teaching and Research Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom. g.turchiano@ucl.ac.uk.ORCID http://orcid.org/0000-0001-9980-6810

Funding

Wellcome TrustWellcome Trust (Wellcome) 217112/Z/19/Z
6 · The paper itself

Abstract

DNA repair mechanisms in human primary cells, including error-free repair, and, recurrent nuclease cleavage events, remain largely uncharacterised. We elucidate gene-editing related repair processes using Cleavage and Lesion Evaluation via Absolute Real-time dPCR (CLEAR-time dPCR), an ensemble of multiplexed dPCR assays that quantifies genome integrity at targeted sites. Utilising CLEAR-time dPCR we track active DSBs, small indels, large deletions, and other aberrations in absolute terms in clinically relevant edited cells, including HSPCs, iPSCs, and T-cells. By quantifying up to 90% of loci with unresolved DSBs, CLEAR-time dPCR reveals biases inherent to conventional mutation screening assays. Furthermore, we accurately quantify DNA repair precision, revealing prevalent scarless repair after blunt and staggered end DSBs and recurrent nucleases cleavage. This work provides one of the most precise analyses of DNA repair and mutation dynamics, paving the way for mechanistic studies to advance gene therapy, designer editors, and small molecule discovery.

Indexed as

DNA RepairEndonucleasesT-LymphocytesCRISPR-Cas SystemsDNA Breaks, Double-StrandedGene EditingHumansInduced Pluripotent Stem CellsMutationEndonucleases

Identifiers

PMID41184307
PMCPMC12583642

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.