Hosseini Sayedeh Azimeh, Salehifard Jouneghani Alizamen, Ghatrehsamani Mahdi, Yaghoobi Hajar, Elahian Fatemeh, Mirzaei Seyed Abbas
Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Pediatrics, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Int J Biol Macromol. 2022 Dec 31;223(Pt A):732-754. doi: 10.1016/j.ijbiomac.2022.11.018. Epub 2022 Nov 11.
Gastrointestinal cancer (GI) is one of the most serious and health-threatening diseases worldwide. Many countries have encountered an escalating prevalence of shock. Therefore, there is a pressing need to clarify the molecular pathogenesis of these cancers. The use of high-throughput technologies that allow the precise and simultaneous investigation of thousands of genes, proteins, and metabolites is a critical step in disease diagnosis and cure. Recent innovations have provided easy and reliable methods for genome investigation, including TALENs, ZFNs, and the CRISPR/Cas9 (clustered regularly interspaced palindromic repeats system). Among these, CRISPR/Cas9 has been revolutionary tool in genetic research. Recent years were prosperous years for CRISPR by the discovery of novel Cas enzymes, the Nobel Prize, and the development of critical clinical trials. This technology utilizes comprehensive information on genes associated with tumor development, provides high-throughput libraries for tumor therapy by developing screening platforms, and generates rapid tools for cancer therapy. This review discusses the various applications of CRISPR/Cas9 in genome editing, with a particular focus on genome manipulation, including infection-related genes, RNAi targets, pooled library screening for identification of unknown driver mutations, and molecular targets for gastrointestinal cancer modeling. Finally, it provides an overview of CRISPR/Cas9 clinical trials, as well as the challenges associated with its use.
胃肠道癌（GI）是全球最严重且威胁健康的疾病之一。许多国家都面临着休克患病率不断上升的问题。因此，迫切需要阐明这些癌症的分子发病机制。使用能够精确且同时检测数千个基因、蛋白质和代谢物的高通量技术是疾病诊断和治疗的关键一步。最近的创新为基因组研究提供了简便可靠的方法，包括转录激活样效应因子核酸酶（TALENs）、锌指核酸酶（ZFNs）和规律成簇间隔短回文重复序列系统（CRISPR/Cas9）。其中，CRISPR/Cas9已成为基因研究中的革命性工具。近年来，随着新型Cas酶的发现、诺贝尔奖的获得以及关键临床试验的开展，CRISPR迎来了繁荣发展的时期。这项技术利用与肿瘤发展相关的基因的全面信息，通过开发筛选平台为肿瘤治疗提供高通量文库，并为癌症治疗生成快速工具。本综述讨论了CRISPR/Cas9在基因组编辑中的各种应用，特别关注基因组操作，包括感染相关基因、RNA干扰靶点、用于鉴定未知驱动突变的混合文库筛选以及胃肠道癌建模的分子靶点。最后，它概述了CRISPR/Cas9的临床试验以及与其使用相关的挑战。
