| Literature DB >> 32783942 |
Peng Zhou1, Becky K C Chan1, Yuk Kei Wan1, Chaya T L Yuen1, Gigi C G Choi1, Xinran Li2, Cindy S W Tong1, Sophia S W Zhong1, Jieran Sun1, Yufan Bao3, Silvia Y L Mak4, Maggie Z Y Chow4, Jien Vei Khaw1, Suet Yi Leung5, Zongli Zheng6, Lydia W T Cheung2, Kaeling Tan7, Koon Ho Wong8, H Y Edwin Chan9, Alan S L Wong10.
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.Entities:
Keywords: CRISPR; CombiGEM; Parkinson's disease; cancer; combination therapy; combinatorial genetics; drug interaction; genetic interaction; high-throughput screening; neurodegeneration
Year: 2020 PMID： 32783942 DOI： 10.1016/j.celrep.2020.108020
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423