Evidence map›Paper›PMID 33479216›Full record

ArticleNature communications2021

Universal toxin-based selection for precise genome engineering in human cells.

Songyuan Li, Nina Akrap, Silvia Cerboni, Michelle J Porritt, Sandra Wimberger, Anders Lundin, Carl Möller, Mike Firth, Euan Gordon, Bojana Lazovic and 12 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  8. AnBioengineering & translational medicine · 2025
    Article
  9. Article
  10. Repair Drive improves gene editing in the liver.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Enrichment strategies to enhance genome editing.Journal of biomedical science · 2023
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 7 institutions in 6 countries.

Songyuan LiTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. songyuan.li@astrazeneca.com.ORCID http://orcid.org/0000-0003-2085-9253
Nina Akrap *Translational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Silvia Cerboni *Translational Science and Experimental Medicine, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Michelle J PorrittTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-1700-0085
Sandra WimbergerTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Anders LundinTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-3131-8022
Carl MöllerTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Mike FirthR&D Data Infrastructure & Tools, AstraZeneca, Cambridge, UK.
Euan GordonDiscovery Biology SWE, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Bojana LazovicTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Aleksandra SieńskaTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Luna Simona PaneTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Matthew A CoelhoWellcome Sanger Institute, Cambridge, UK.ORCID http://orcid.org/0000-0003-3737-2468
Giovanni CiottaDiscovery Biology UK, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Giovanni PellegriniCVRM pathology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Marcella SiniCVRM pathology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Xiufeng XuDepartment of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden.
Suman MitraInserm UMR1277 CNRS UMR9020 - CANTHER, Institut pour la Recherche sur le Cancer de Lille, Lille, France.ORCID http://orcid.org/0000-0002-3426-371X
Mohammad Bohlooly-YTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Benjamin J M TaylorDiscovery Biology UK, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID http://orcid.org/0000-0001-6101-3786
Grzegorz SienskiTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. grzegorz.sienski@astrazeneca.com.ORCID http://orcid.org/0000-0002-2730-7710
Marcello MarescaTranslational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. Marcello.Maresca@astrazeneca.com.ORCID http://orcid.org/0000-0003-0796-661X
AstraZeneca (Sweden) · SEAstraZeneca (United Kingdom) · GBAstraZeneca (Japan) · JPAstraZeneca (Australia) · AUCentre National de la Recherche Scientifique · FRKarolinska Institutet · SEWellcome Sanger Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems.

Indexed as

CRISPR-Cas SystemsMutationAnimalsCD4-Positive T-LymphocytesCell ProliferationCells, CulturedCell SurvivalGene EditingGenetic EngineeringHCT116 CellsHEK293 CellsHeparin-binding EGF-like Growth FactorHumansInduced Pluripotent Stem CellsMiceHeparin-binding EGF-like Growth Factor

Identifiers

PMID33479216
PMCPMC7820243
OpenAlexW3121904305

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.