Evidence map›Paper›PMID 39633028›Full record

ArticleNature biomedical engineering2025

Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes.

Jiang-An Yin, Lukas Frick, Manuel C Scheidmann, Tingting Liu, Chiara Trevisan, Ashutosh Dhingra, Anna Spinelli, Yancheng Wu, Longping Yao, Dalila Laura Vena and 24 more

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

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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

34 authors.

Jiang-An Yin *Institute of Neuropathology, University of Zurich, Zurich, Switzerland. jiang-an.yin@uzh.ch.ORCID 0000-0002-2134-8693
Lukas Frick *Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
Manuel C ScheidmannNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.
Tingting LiuInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Chiara TrevisanInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-3997-094X
Ashutosh DhingraGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Anna SpinelliInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Yancheng WuInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-2809-4865
Longping YaoInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Dalila Laura VenaInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.ORCID 0009-0007-6863-7349
Britta KnappNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.
Jingjing GuoInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Elena De CeccoInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Kathi GingInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Andrea ArmaniInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-4765-9748
Edward J OakeleyNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.ORCID 0000-0001-6226-7470
Florian NigschNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.ORCID 0000-0002-2919-8749
Joel JenzerNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.
Jasmin HaegeleNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.
Michal PikusaNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.
Joachim TägerGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Salvador Rodriguez-NietoGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Vangelis BourisInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Rafaela RibeiroInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Federico BaroniInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Manmeet Sakshi BediNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.
Scott BerryDepartment of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Marco LosaInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-3428-418X
Simone HornemannInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-2674-9891
Martin KampmannInstitute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
Lucas PelkmansDepartment of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Dominic HoepfnerNovartis Institutes for Biomedical Research, Novartis Campus, Basel, Switzerland.
Peter HeutinkGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Adriano AguzziInstitute of Neuropathology, University of Zurich, Zurich, Switzerland. adriano.aguzzi@uzh.ch.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Arrayed CRISPR libraries extend the scope of gene-perturbation screens to non-selectable cell phenotypes. However, library generation requires assembling thousands of vectors expressing single-guide RNAs (sgRNAs). Here, by leveraging massively parallel plasmid-cloning methodology, we show that arrayed libraries can be constructed for the genome-wide ablation (19,936 plasmids) of human protein-coding genes and for their activation and epigenetic silencing (22,442 plasmids), with each plasmid encoding an array of four non-overlapping sgRNAs designed to tolerate most human DNA polymorphisms. The quadruple-sgRNA libraries yielded high perturbation efficacies in deletion (75-99%) and silencing (76-92%) experiments and substantial fold changes in activation experiments. Moreover, an arrayed activation screen of 1,634 human transcription factors uncovered 11 novel regulators of the cellular prion protein PrP

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGene LibraryGene SilencingGenome, HumanGene DeletionHEK293 CellsHumansPlasmidsRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39633028
PMCPMC11754104

What OpenQuestion holds

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LicenceCC BY
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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.