TY  - JOUR
AU  - Yin, Jiang-An
AU  - Frick, Lukas
AU  - Scheidmann, Manuel C
AU  - Liu, Tingting
AU  - Trevisan, Chiara
AU  - Dhingra, Ashutosh
AU  - Spinelli, Anna
AU  - Wu, Yancheng
AU  - Yao, Longping
AU  - Vena, Dalila Laura
AU  - Knapp, Britta
AU  - Guo, Jingjing
AU  - De Cecco, Elena
AU  - Ging, Kathi
AU  - Armani, Andrea
AU  - Oakeley, Edward J
AU  - Nigsch, Florian
AU  - Jenzer, Joel
AU  - Haegele, Jasmin
AU  - Pikusa, Michal
AU  - Täger, Joachim
AU  - Rodriguez-Nieto, Salvador
AU  - Bouris, Vangelis
AU  - Ribeiro, Rafaela
AU  - Baroni, Federico
AU  - Bedi, Manmeet Sakshi
AU  - Berry, Scott
AU  - Losa, Marco
AU  - Hornemann, Simone
AU  - Kampmann, Martin
AU  - Pelkmans, Lucas
AU  - Hoepfner, Dominic
AU  - Heutink, Peter
AU  - Aguzzi, Adriano
TI  - Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes.
JO  - Nature biomedical engineering
VL  - 9
IS  - 1
SN  - 2157-846X
CY  - Tokyo
PB  - Nature Research
M1  - DZNE-2025-00230
SP  - 127 - 148
PY  - 2025
AB  - 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
KW  - Humans
KW  - Gene Silencing
KW  - CRISPR-Cas Systems: genetics
KW  - Genome, Human: genetics
KW  - Gene Library
KW  - RNA, Guide, CRISPR-Cas Systems: genetics
KW  - Plasmids: genetics
KW  - Gene Deletion
KW  - HEK293 Cells
KW  - Clustered Regularly Interspaced Short Palindromic Repeats: genetics
KW  - Transcription Factors: genetics
KW  - Transcription Factors: metabolism
KW  - RNA, Guide, CRISPR-Cas Systems (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39633028
DO  - DOI:10.1038/s41551-024-01278-4
UR  - https://pub.dzne.de/record/276158
ER  -