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@ARTICLE{Yin:276158,
      author       = {Yin, Jiang-An and Frick, Lukas and Scheidmann, Manuel C and
                      Liu, Tingting and Trevisan, Chiara and Dhingra, Ashutosh and
                      Spinelli, Anna and Wu, Yancheng and Yao, Longping and Vena,
                      Dalila Laura and Knapp, Britta and Guo, Jingjing and De
                      Cecco, Elena and Ging, Kathi and Armani, Andrea and Oakeley,
                      Edward J and Nigsch, Florian and Jenzer, Joel and Haegele,
                      Jasmin and Pikusa, Michal and Täger, Joachim and
                      Rodriguez-Nieto, Salvador and Bouris, Vangelis and Ribeiro,
                      Rafaela and Baroni, Federico and Bedi, Manmeet Sakshi and
                      Berry, Scott and Losa, Marco and Hornemann, Simone and
                      Kampmann, Martin and Pelkmans, Lucas and Hoepfner, Dominic
                      and Heutink, Peter and Aguzzi, Adriano},
      title        = {{A}rrayed {CRISPR} libraries for the genome-wide
                      activation, deletion and silencing of human protein-coding
                      genes.},
      journal      = {Nature biomedical engineering},
      volume       = {9},
      number       = {1},
      issn         = {2157-846X},
      address      = {Tokyo},
      publisher    = {Nature Research},
      reportid     = {DZNE-2025-00230},
      pages        = {127 - 148},
      year         = {2025},
      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
                      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.},
      keywords     = {Humans / Gene Silencing / CRISPR-Cas Systems: genetics /
                      Genome, Human: genetics / Gene Library / RNA, Guide,
                      CRISPR-Cas Systems: genetics / Plasmids: genetics / Gene
                      Deletion / HEK293 Cells / Clustered Regularly Interspaced
                      Short Palindromic Repeats: genetics / Transcription Factors:
                      genetics / Transcription Factors: metabolism / RNA, Guide,
                      CRISPR-Cas Systems (NLM Chemicals) / Transcription Factors
                      (NLM Chemicals)},
      cin          = {AG Heutink / AG Täger},
      ddc          = {610},
      cid          = {I:(DE-2719)1210002 / I:(DE-2719)5000002},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354) / 899
                      - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39633028},
      doi          = {10.1038/s41551-024-01278-4},
      url          = {https://pub.dzne.de/record/276158},
}