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000276158 1001_ $$0P:(DE-2719)9002756$$aYin, Jiang-An$$b0
000276158 245__ $$aArrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes.
000276158 260__ $$aTokyo$$bNature Research$$c2025
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000276158 520__ $$aArrayed 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 PrPC, screening with a pooled version of the ablation library led to the identification of 5 novel modifiers of autophagy that otherwise went undetected, and 'post-pooling' individually produced lentiviruses eliminated template-switching artefacts and enhanced the performance of pooled screens for epigenetic silencing. Quadruple-sgRNA arrayed libraries are a powerful and versatile resource for targeted genome-wide perturbations.
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000276158 650_7 $$2NLM Chemicals$$aRNA, Guide, CRISPR-Cas Systems
000276158 650_7 $$2NLM Chemicals$$aTranscription Factors
000276158 650_2 $$2MeSH$$aHumans
000276158 650_2 $$2MeSH$$aGene Silencing
000276158 650_2 $$2MeSH$$aCRISPR-Cas Systems: genetics
000276158 650_2 $$2MeSH$$aGenome, Human: genetics
000276158 650_2 $$2MeSH$$aGene Library
000276158 650_2 $$2MeSH$$aRNA, Guide, CRISPR-Cas Systems: genetics
000276158 650_2 $$2MeSH$$aPlasmids: genetics
000276158 650_2 $$2MeSH$$aGene Deletion
000276158 650_2 $$2MeSH$$aHEK293 Cells
000276158 650_2 $$2MeSH$$aClustered Regularly Interspaced Short Palindromic Repeats: genetics
000276158 650_2 $$2MeSH$$aTranscription Factors: genetics
000276158 650_2 $$2MeSH$$aTranscription Factors: metabolism
000276158 7001_ $$aFrick, Lukas$$b1
000276158 7001_ $$aScheidmann, Manuel C$$b2
000276158 7001_ $$aLiu, Tingting$$b3
000276158 7001_ $$00000-0002-3997-094X$$aTrevisan, Chiara$$b4
000276158 7001_ $$0P:(DE-2719)2811729$$aDhingra, Ashutosh$$b5$$udzne
000276158 7001_ $$aSpinelli, Anna$$b6
000276158 7001_ $$00000-0003-2809-4865$$aWu, Yancheng$$b7
000276158 7001_ $$aYao, Longping$$b8
000276158 7001_ $$00009-0007-6863-7349$$aVena, Dalila Laura$$b9
000276158 7001_ $$aKnapp, Britta$$b10
000276158 7001_ $$aGuo, Jingjing$$b11
000276158 7001_ $$aDe Cecco, Elena$$b12
000276158 7001_ $$aGing, Kathi$$b13
000276158 7001_ $$00000-0002-4765-9748$$aArmani, Andrea$$b14
000276158 7001_ $$00000-0001-6226-7470$$aOakeley, Edward J$$b15
000276158 7001_ $$00000-0002-2919-8749$$aNigsch, Florian$$b16
000276158 7001_ $$aJenzer, Joel$$b17
000276158 7001_ $$aHaegele, Jasmin$$b18
000276158 7001_ $$aPikusa, Michal$$b19
000276158 7001_ $$0P:(DE-2719)2811804$$aTäger, Joachim$$b20$$udzne
000276158 7001_ $$0P:(DE-2719)2812129$$aRodriguez-Nieto, Salvador$$b21$$udzne
000276158 7001_ $$aBouris, Vangelis$$b22
000276158 7001_ $$aRibeiro, Rafaela$$b23
000276158 7001_ $$aBaroni, Federico$$b24
000276158 7001_ $$aBedi, Manmeet Sakshi$$b25
000276158 7001_ $$aBerry, Scott$$b26
000276158 7001_ $$00000-0003-3428-418X$$aLosa, Marco$$b27
000276158 7001_ $$00000-0002-2674-9891$$aHornemann, Simone$$b28
000276158 7001_ $$aKampmann, Martin$$b29
000276158 7001_ $$aPelkmans, Lucas$$b30
000276158 7001_ $$aHoepfner, Dominic$$b31
000276158 7001_ $$0P:(DE-2719)2810728$$aHeutink, Peter$$b32
000276158 7001_ $$aAguzzi, Adriano$$b33
000276158 773__ $$0PERI:(DE-600)2878897-7$$a10.1038/s41551-024-01278-4$$gVol. 9, no. 1, p. 127 - 148$$n1$$p127 - 148$$tNature biomedical engineering$$v9$$x2157-846X$$y2025
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