Shojaei Baghini Sadegh, Gardanova Zhanna R, Zekiy Angelina Olegovna, Shomali Navid, Tosan Foad, Jarahian Mostafa
Plant Biotechnology Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Department of Psychotherapy, Pirogov Russian National Research Medical University, Moscow, Russia.
Front Bioeng Biotechnol. 2021 Nov 19;9:775309. doi: 10.3389/fbioe.2021.775309. eCollection 2021.
During recent years, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technologies have been noticed as a rapidly evolving tool to deliver a possibility for modifying target sequence expression and function. The CRISPR/Cas9 tool is currently being used to treat a myriad of human disorders, ranging from genetic diseases and infections to cancers. Preliminary reports have shown that CRISPR technology could result in valued consequences for the treatment of Duchenne muscular dystrophy (DMD), cystic fibrosis (CF), β-thalassemia, Huntington's diseases (HD), etc. Nonetheless, high rates of off-target effects may hinder its application in clinics. Thereby, recent studies have focused on the finding of the novel strategies to ameliorate these off-target effects and thereby lead to a high rate of fidelity and accuracy in human, animals, prokaryotes, and also plants. Meanwhile, there is clear evidence indicating that the design of the specific sgRNA with high efficiency is of paramount importance. Correspondingly, elucidation of the principal parameters that contributed to determining the sgRNA efficiencies is a prerequisite. Herein, we will deliver an overview regarding the therapeutic application of CRISPR technology to treat human disorders. More importantly, we will discuss the potent influential parameters (e.g., sgRNA structure and feature) implicated in affecting the sgRNA efficacy in CRISPR/Cas9 technology, with special concentration on human and animal studies.
近年来,成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9(Cas9)技术已成为一种快速发展的工具,为改变靶序列的表达和功能提供了可能。CRISPR/Cas9工具目前正被用于治疗多种人类疾病,从遗传疾病、感染到癌症。初步报告显示,CRISPR技术可能会给杜氏肌营养不良症(DMD)、囊性纤维化(CF)、β地中海贫血、亨廷顿舞蹈症(HD)等疾病的治疗带来有价值的成果。尽管如此,高脱靶率可能会阻碍其在临床中的应用。因此,最近的研究集中在寻找新的策略来改善这些脱靶效应,从而在人类、动物、原核生物以及植物中实现高保真度和准确性。同时,有明确证据表明设计高效的特异性sgRNA至关重要。相应地,阐明有助于确定sgRNA效率的主要参数是一个先决条件。在此,我们将概述CRISPR技术在治疗人类疾病方面的治疗应用。更重要的是,我们将讨论在CRISPR/Cas9技术中影响sgRNA功效的潜在影响参数(如sgRNA结构和特征),特别关注人类和动物研究。