Aptazyme-mediated direct modulation of post-transcriptional sgRNA level for conditional genome editing and gene expression
Aptazyme-mediated direct modulation of post-transcriptional sgRNA level for conditional genome editing and gene expression
复制标题
适体酶介导的转录后 sgRNA 水平的直接调节用于条件基因组编辑和基因表达
DOI：
10.1016/j.jbiotec.2018.10.011
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发表时间：
2018-12-20
影响因子：
4.1
通讯作者：
Xia, Haibin
中科院分区：
文献类型：
--
作者：
Chen, Hao;Li, Yanqing;Xia, Haibin
来源于微生物CRISPR-Cas适应性免疫系统的RNA引导的核酸内切酶Cas9是基因组编辑的有力工具，已广泛应用于真核系统、原核系统和植物中。然而，Cas9/sgRNA引起的脱靶效应仍然是一个主要问题。目前，减少脱靶效应的努力主要集中在提高sgRNA/Cas9的靶向特异性、调节Cas9蛋白或sgRNA的活性以及控制其表达的时间窗口上。本研究建立了一个新的小分子适体酶调控转录后sgRNA水平的系统。该系统被证明可以减少Cas9/sgRNA引起的脱靶效应，同时能够对基因编辑和调控活性进行精确的时间控制。这个新系统可以为基因组编辑和治疗应用提供一个潜在的更安全，更强大的工具。
RNA-guided endonuclease Cas9 derived from microbial CRISPR-Cas adaptive immune systems is a powerful tool for genome editing, which has been widely used in eukaryotic systems, prokaryotic systems, and plants. However, the off-target effects caused by Cas9/sgRNA remain a major concern. Currently, the efforts to reduce the off-target effects mainly focus on improving the targeting specificity of sgRNA/Cas9, regulating the activity of the Cas9 protein or the sgRNA, and controlling the time window of their expression. In this study, a novel system was established to regulate the post-transcriptional sgRNA level by small molecule-controlled aptazyme. This system was shown to reduce the off-target effects caused by Cas9/sgRNA, while enabling precise temporal control over gene editing and regulatory activity. This new system could provide a potentially safer and more powerful tool for genome editing and therapeutic application.