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

Autor: Peng Zhou, Becky K.C. Chan, Yuk Kei Wan, Chaya T.L. Yuen, Gigi C.G. Choi, Xinran Li, Cindy S.W. Tong, Sophia S.W. Zhong, Jieran Sun, Yufan Bao, Silvia Y.L. Mak, Maggie Z.Y. Chow, Jien Vei Khaw, Suet Yi Leung, Zongli Zheng, Lydia W.T. Cheung, Kaeling Tan, Koon Ho Wong, H.Y. Edwin Chan, Alan S.L. Wong
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Reports, Vol 32, Iss 6, Pp 108020- (2020)
Druh dokumentu: article
ISSN: 2211-1247
12342599
DOI: 10.1016/j.celrep.2020.108020
Popis: Summary: 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.
Databáze: Directory of Open Access Journals