A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets.

Autor:	Zhou P; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Chan BKC; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Wan YK; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Yuen CTL; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Choi GCG; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Li X; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Tong CSW; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Zhong SSW; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Sun J; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Bao Y; Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China., Mak SYL; Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Hong Kong SAR, China., Chow MZY; Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Hong Kong SAR, China., Khaw JV; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Leung SY; Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; Centre for PanorOmic Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; The Jockey Club Centre for Clinical Innovation and Discovery, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Zheng Z; Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; Biotechnology and Health Centre, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China., Cheung LWT; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Tan K; Faculty of Health Sciences, University of Macau, Macau SAR, China; Genomics, Bioinformatics and Single Cell Analysis Core, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China., Wong KH; Faculty of Health Sciences, University of Macau, Macau SAR, China; Institute of Translational Medicine, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China., Chan HYE; Laboratory of Drosophila Research, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Hong Kong SAR, China., Wong ASL; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Electronic address: aslw@hku.hk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Aug 11; Vol. 32 (6), pp. 108020.
DOI:	10.1016/j.celrep.2020.108020
Abstrakt:	We present a CRISPR-based multi-gene knockout screening system and toolkits for extensible assembly of barcoded high-order combinatorial guide RNA libraries en masse. We apply this system for systematically identifying not only pairwise but also three-way synergistic therapeutic target combinations and successfully validate double- and triple-combination regimens for suppression of cancer cell growth and protection against Parkinson's disease-associated toxicity. This system overcomes the practical challenges of experimenting on a large number of high-order genetic and drug combinations and can be applied to uncover the rare synergistic interactions between druggable targets. Competing Interests: Declaration of Interests The authors have filed a patent application based on this work. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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