Asmamaw Mengstie Misganaw, Teshome Azezew Muluken, Asmamaw Dejenie Tadesse, Teshome Assefa Agegnehu, Tadele Admasu Fitalew, Behaile Teklemariam Awgichew, Tilahun Mulu Anemut, Mekonnen Agidew Melaku, Adugna Dagnew Getnet, Geremew Habtamu, Abebe Endeshaw Chekol
Department of Biochemistry, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia.
Department of Physiology, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia.
Biologics. 2024 Jan 18;18:21-28. doi: 10.2147/BTT.S429411. eCollection 2024.
The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.
CRISPR-Cas（成簇规律间隔短回文重复序列（CRISPR））及相关蛋白（Cas9）系统是一种虽新但已得到充分研究的基因组编辑工具，有望为多种遗传疾病提供解决方案。具有20个碱基的用户定义间隔序列的单向导RNA（sgRNA）和Cas9核酸内切酶构成了CRISPR-Cas9系统的核心。这种sgRNA可将Cas9核酸酶导向任何基因组区域，该区域下游紧邻原间隔序列邻近基序（PAM）且与间隔序列匹配。CRISPR-Cas9基因组编辑技术临床应用中的当前挑战是可能产生的脱靶效应，即可能导致在错误位点切割DNA。脱靶基因组编辑除了可能使关于基因活性的科学发现受到质疑外，还会混淆并降低CRISPR-Cas9的治疗潜力。在本综述中，我们总结了近期在降低CRISPR-Cas9基因组编辑脱靶效应方面的技术进展。
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