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CRISPR-Cas9 文库筛选方法在抗癌药物发现中的应用:概述与展望。

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

机构信息

School of Chinese Medicine, The University of Hong Kong.

School of Chinese Medicine, Hong Kong Baptist University.

出版信息

Theranostics. 2022 Apr 11;12(7):3329-3344. doi: 10.7150/thno.71144. eCollection 2022.

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.

摘要

CRISPR-Cas9 是一项获得诺贝尔奖的强大基因编辑工具,它是在过去十年中开发的。这项技术可以在所有生物的基因组上实现高精度的稳定基因工程方法。该技术的最新进展包括基因组文库筛选方法,可以通过功能获得或丧失来检测生存必需和耐药基因。这种多功能的机制允许进行基因组筛选以激活或抑制基因,并靶向非编码序列,如启动子、miRNA 和 lncRNA。在这篇综述中,我们介绍了新兴的高通量 CRISPR-Cas9 文库基因组筛选技术及其工作原理,通过正负选择来检测生存和耐药基因。该技术与其他现有方法进行了比较,同时重点介绍了其在抗癌药物发现中的各种应用的优势,包括功能和靶标鉴定、非编码 RNA 信息、小分子作用以及药物靶标发现。CRISPR-Cas9 系统与多组学平台的结合代表了一个充满活力的领域,有望推动抗癌药物发现和临床精准医学的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7654/9065202/50798b2b7743/thnov12p3329g001.jpg

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