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

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.

Design and synthesis of APN and 3CLpro dual‐target inhibitors based on STSBPT with anticoronavirus activity

“…Usually, drug-target discovery work is mainly based on omics (including genomics, proteomics, metabolomics and transcriptomics), mass spectrometry, CRISPR-based gene editing and computational approaches (including network-based, machine learning and molecular docking simulation approaches). [44][45][46][47] However, these methods have limitations in terms of exploring drug targets with similar functions or structures. It is common for drugs to have multiple targets in vivo, even if they were originally designed to target a single specific target.…”

“…The DTD‐STSBPT introduces a novel perspective to the methodology of identifying secondary drug targets beyond the primary target. Usually, drug–target discovery work is mainly based on omics (including genomics, proteomics, metabolomics and transcriptomics), mass spectrometry, CRISPR‐based gene editing and computational approaches (including network‐based, machine learning and molecular docking simulation approaches) 44–47 . However, these methods have limitations in terms of exploring drug targets with similar functions or structures.…”

Multi-component Chinese medicine formulas for drug discovery: State of the art and future perspectives

“…CRISPR technology uses an anti-viral defense enzyme found in bacteria and a guide RNA to locate gene-editing targets [101]. This platform, for which a Nobel prize has been awarded, is now widely used in various disease models, including inherited gene defects and cancers [102]. It is also applied in disease detection and diagnosis, genetically modified foods, and farming [103,104].…”

Nanotechnology‐based CRISPR/Cas9 delivery system for genome editing in cancer treatment

“…24,[32][33][34] Different CRISPR/ Cas9-mediated cancer therapy approaches, such as altering chemo-tolerance genes, changing metabolically relevant genes and tumor stem cell associated genes, as well as cancer immunotherapy, are well-established in diverse cancer types. 32,[35][36][37][38] Although the discovery of CRISPR/Cas9 paved the way for simple, effective, and multiplex manipulation of genes, the off-target impacts, difficulties in targeting specific cells in vivo, and the successful transfer into the nuclei still remain the main obstacles keeping it from realizing its maximum capabilities. 39,40 Rational delivery systems and improvements in the CRISPR/Cas9 genome engineering technique may be able to solve these problems.…”

“…Given its promising potential in gene therapy, CRISPR/Cas9 has expanded rapidly in biomedical research of cancer treatment 24,32–34 . Different CRISPR/Cas9‐mediated cancer therapy approaches, such as altering chemo‐tolerance genes, changing metabolically relevant genes and tumor stem cell associated genes, as well as cancer immunotherapy, are well‐established in diverse cancer types 32,35–38 . Although the discovery of CRISPR/Cas9 paved the way for simple, effective, and multiplex manipulation of genes, the off‐target impacts, difficulties in targeting specific cells in vivo, and the successful transfer into the nuclei still remain the main obstacles keeping it from realizing its maximum capabilities 39,40 .…”