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A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets
Zhou,Peng1; Chan,Becky K.C.1; Wan,Yuk Kei1; Yuen,Chaya T.L.1; Choi,Gigi C.G.1; Li,Xinran2; Tong,Cindy S.W.1; Zhong,Sophia S.W.1; Sun,Jieran1; Bao,Yufan3,4; Mak,Silvia Y.L.3; Chow,Maggie Z.Y.3; Khaw,Jien Vei1; Leung,Suet Yi5,6,7; Zheng,Zongli3,4,8; Cheung,Lydia W.T.2; Tan,Kaeling9,10; Wong,Koon Ho9,11; Chan,H. Y.Edwin12,13; Wong,Alan S.L.1,14
2020-08-11
Source PublicationCell Reports
ISSN2211-1247
Volume32Issue:6
Abstract

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.

KeywordCancer Combigem Combination Therapy Combinatorial Genetics Crispr Drug Interaction Genetic Interaction High-throughput Screening Neurodegeneration Parkinson's Disease
DOI10.1016/j.celrep.2020.108020
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000560042600017
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorWong,Alan S.L.
Affiliation1.Laboratory of Combinatorial Genetics and Synthetic Biology,School of Biomedical Sciences,The University of Hong Kong,Hong Kong SAR,Pokfulam,Hong Kong
2.School of Biomedical Sciences,The University of Hong Kong,Hong Kong SAR,Pokfulam,Hong Kong
3.Ming Wai Lau Centre for Reparative Medicine,Karolinska Institutet,Hong Kong SAR,Hong Kong
4.Department of Biomedical Sciences,City University of Hong Kong,Hong Kong SAR,Hong Kong
5.Department of Pathology,The University of Hong Kong,Hong Kong SAR,Pokfulam,Hong Kong
6.Centre for PanorOmic Sciences,The University of Hong Kong,Hong Kong SAR,Pokfulam,Hong Kong
7.The Jockey Club Centre for Clinical Innovation and Discovery,LKS Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,Pokfulam,Hong Kong
8.Biotechnology and Health Centre,City University of Hong Kong Shenzhen Research Institute,Shenzhen,China
9.Faculty of Health Sciences,University of Macau,Macau SAR,China
10.Genomics,Bioinformatics and Single Cell Analysis Core,Faculty of Health Sciences,University of Macau,Avenida da Universidade,Taipa,Macau SAR,China
11.Institute of Translational Medicine,University of Macau,Avenida da Universidade,Taipa,Macau SAR,China
12.Laboratory of Drosophila Research,School of Life Sciences,The Chinese University of Hong Kong,Hong Kong SAR,Hong Kong
13.Gerald Choa Neuroscience Centre,The Chinese University of Hong Kong,Hong Kong SAR,Hong Kong
14.Department of Electrical and Electronic Engineering,The University of Hong Kong,Hong Kong SAR,Pokfulam,Hong Kong
Recommended Citation
GB/T 7714
Zhou,Peng,Chan,Becky K.C.,Wan,Yuk Kei,et al. A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets[J]. Cell Reports,2020,32(6).
APA Zhou,Peng,Chan,Becky K.C.,Wan,Yuk Kei,Yuen,Chaya T.L.,Choi,Gigi C.G.,Li,Xinran,Tong,Cindy S.W.,Zhong,Sophia S.W.,Sun,Jieran,Bao,Yufan,Mak,Silvia Y.L.,Chow,Maggie Z.Y.,Khaw,Jien Vei,Leung,Suet Yi,Zheng,Zongli,Cheung,Lydia W.T.,Tan,Kaeling,Wong,Koon Ho,Chan,H. Y.Edwin,&Wong,Alan S.L..(2020).A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets.Cell Reports,32(6).
MLA Zhou,Peng,et al."A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets".Cell Reports 32.6(2020).
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