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; 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

doi:10.1016/j.celrep.2020.108020

Author(s)

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
Silvia Y.L. Mak
Maggie Z.Y. Chow
Jien Vei Khaw
Suet Yi Leung
Lydia W.T. Cheung
Kaeling Tan
Koon Ho Wong
H.Y. Edwin Chan
Alan S.L. Wong

Related Research Unit(s)

Detail(s)

Original language	English
Article number	108020
Journal / Publication	Cell Reports
Volume	32
Issue number	6
Online published	11 Aug 2020
Publication status	Published - 11 Aug 2020

Link(s)

DOI	DOI https://doi.org/10.1016/j.celrep.2020.108020 Final Published version
	Check@CityULib
Attachment(s)	Documents 55870048.pdf Final Published version, 5.64 MB, PDF Publisher's Copyright Statement This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/
Link to Scopus	https://www.scopus.com/record/display.uri?eid=2-s2.0-85089183838&origin=recordpage
Permanent Link	https://scholars.cityu.edu.hk/en/publications/publication(8830a940-96db-456e-bbf7-2f4fe7bc7922).html

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.

Research Area(s)

cancer, CombiGEM, combination therapy, combinatorial genetics, CRISPR, drug interaction, genetic interaction, high-throughput screening, neurodegeneration, Parkinson's disease

Citation Format(s)

[ RIS ] [ BibTeX ]

A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets. / Zhou, Peng; Chan, Becky K.C.; Wan, Yuk Kei et al.
In: Cell Reports, Vol. 32, No. 6, 108020, 11.08.2020.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review

Zhou, P, Chan, BKC, Wan, YK, Yuen, CTL, Choi, GCG, Li, X, Tong, CSW, Zhong, SSW, Sun, J, Bao, Y, Mak, SYL, Chow, MZY, Khaw, JV, Leung, SY, Zheng, Z, Cheung, LWT, Tan, K, Wong, KH, Chan, HYE & Wong, ASL 2020, 'A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets', Cell Reports, vol. 32, no. 6, 108020. https://doi.org/10.1016/j.celrep.2020.108020

Zhou, P., Chan, B. K. C., Wan, Y. K., Yuen, C. T. L., Choi, G. C. G., Li, X., Tong, C. S. W., Zhong, S. S. W., Sun, J., Bao, Y., Mak, S. Y. L., Chow, M. Z. Y., Khaw, J. V., Leung, S. Y., Zheng, Z., Cheung, L. W. T., Tan, K., Wong, K. H., Chan, H. Y. E., & Wong, A. S. L. (2020). A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets. Cell Reports, 32(6), Article 108020. Advance online publication. https://doi.org/10.1016/j.celrep.2020.108020

Zhou P, Chan BKC, Wan YK, Yuen CTL, Choi GCG, Li X et al. A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets. Cell Reports. 2020 Aug 11;32(6):108020. Epub 2020 Aug 11. doi: 10.1016/j.celrep.2020.108020

Zhou, Peng ; Chan, Becky K.C. ; Wan, Yuk Kei et al. / A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets. In: Cell Reports. 2020 ; Vol. 32, No. 6.

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