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

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 (+8 others)
2020 Cell Reports  
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
more » ... cal 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.
doi:10.1016/j.celrep.2020.108020 pmid:32783942 fatcat:hjxcaqy4cjcq7jkp2bb3silcj4