Theranostics 2022; 12(7):3329-3344. doi:10.7150/thno.71144 This issue

Review

CRISPR-Cas9 library screening approach for anti-cancer drug discovery: overview and perspectives

Yau-Tuen Chan1, Yuanjun Lu1, Junyu Wu1, Cheng Zhang1, Hor-Yue Tan2, Zhao-xiang Bian2, Ning Wang1✉, Yibin Feng1✉

1. School of Chinese Medicine, The University of Hong Kong.
2. School of Chinese Medicine, Hong Kong Baptist University.

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Citation:
Chan YT, Lu Y, Wu J, Zhang C, Tan HY, Bian Zx, Wang N, Feng Y. CRISPR-Cas9 library screening approach for anti-cancer drug discovery: overview and perspectives. Theranostics 2022; 12(7):3329-3344. doi:10.7150/thno.71144. Available from https://www.thno.org/v12p3329.htm

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Abstract

Graphic abstract

CRISPR-Cas9 is a Nobel Prize-winning robust gene-editing tool developed in the last decade. This technique enables a stable genetic engineering method with high precision on the genomes of all organisms. The latest advances in the technology include a genome library screening approach, which can detect survival-essential and drug resistance genes via gain or loss of function. The versatile machinery allows genomic screening for gene activation or inhibition, and targets non-coding sequences, such as promoters, miRNAs, and lncRNAs. In this review, we introduce the emerging high-throughput CRISPR-Cas9 library genome screening technology and its working principles to detect survival and drug resistance genes through positive and negative selection. The technology is compared with other existing approaches while focusing on the advantages of its variable applications in anti-cancer drug discovery, including functions and target identification, non-coding RNA information, actions of small molecules, and drug target discoveries. The combination of the CRISPR-Cas9 system with multi-omic platforms represents a dynamic field expected to advance anti-cancer drug discovery and precision medicine in the clinic.

Keywords: CRISPR-Cas9, Library screening, Cancer therapy, Drug discovery, Experimental models