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

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^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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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.

Original language	English
Article number	108020
Journal	Cell Reports
Volume	32
Issue number	6
Online published	11 Aug 2020
DOIs	https://doi.org/10.1016/j.celrep.2020.108020
Publication status	Published - 11 Aug 2020

Research Keywords

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

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/

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2020.108020

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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. https://doi.org/10.1016/j.celrep.2020.108020

@article{8830a94096db456ebbf72f4fe7bc7922,

title = "A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets",

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.",

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

author = "Peng Zhou and Chan, {Becky K.C.} and Wan, {Yuk Kei} and Yuen, {Chaya T.L.} and Choi, {Gigi C.G.} and Xinran Li and Tong, {Cindy S.W.} and Zhong, {Sophia S.W.} and Jieran Sun and Yufan Bao and Mak, {Silvia Y.L.} and Chow, {Maggie Z.Y.} and Khaw, {Jien Vei} and Leung, {Suet Yi} and Zongli Zheng and Cheung, {Lydia W.T.} and Kaeling Tan and Wong, {Koon Ho} and Chan, {H.Y. Edwin} and Wong, {Alan S.L.}",

year = "2020",

month = aug,

day = "11",

doi = "10.1016/j.celrep.2020.108020",

language = "English",

volume = "32",

journal = "Cell Reports",

issn = "2639-1856",

publisher = "Elsevier B.V.",

number = "6",

}

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

TY - JOUR

T1 - A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets

AU - Zhou, Peng

AU - Chan, Becky K.C.

AU - Wan, Yuk Kei

AU - Yuen, Chaya T.L.

AU - Choi, Gigi C.G.

AU - Li, Xinran

AU - Tong, Cindy S.W.

AU - Zhong, Sophia S.W.

AU - Sun, Jieran

AU - Bao, Yufan

AU - Mak, Silvia Y.L.

AU - Chow, Maggie Z.Y.

AU - Khaw, Jien Vei

AU - Leung, Suet Yi

AU - Zheng, Zongli

AU - Cheung, Lydia W.T.

AU - Tan, Kaeling

AU - Wong, Koon Ho

AU - Chan, H.Y. Edwin

AU - Wong, Alan S.L.

PY - 2020/8/11

Y1 - 2020/8/11

N2 - 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.

AB - 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.

KW - cancer

KW - CombiGEM

KW - combination therapy

KW - combinatorial genetics

KW - CRISPR

KW - drug interaction

KW - genetic interaction

KW - high-throughput screening

KW - neurodegeneration

KW - Parkinson's disease

KW - cancer

KW - CombiGEM

KW - combination therapy

KW - combinatorial genetics

KW - CRISPR

KW - drug interaction

KW - genetic interaction

KW - high-throughput screening

KW - neurodegeneration

KW - Parkinson's disease

KW - cancer

KW - CombiGEM

KW - combination therapy

KW - combinatorial genetics

KW - CRISPR

KW - drug interaction

KW - genetic interaction

KW - high-throughput screening

KW - neurodegeneration

KW - Parkinson's disease

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85089183838&origin=recordpage

U2 - 10.1016/j.celrep.2020.108020

DO - 10.1016/j.celrep.2020.108020

M3 - RGC 21 - Publication in refereed journal

SN - 2639-1856

VL - 32

JO - Cell Reports

JF - Cell Reports

IS - 6

M1 - 108020

ER -

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

Abstract

Research Keywords

Publisher's Copyright Statement

UN SDGs

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