Zhang Jingfang, Chen Li, Zhang Ju, Wang Yu
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Comput Struct Biotechnol J. 2019 Jul 30;17:1171-1177. doi: 10.1016/j.csbj.2019.07.015. eCollection 2019.
Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems have been employed as a powerful versatile technology for programmable gene editing, transcriptional modulation, epigenetic modulation, and genome labeling, Yet better control of their activity is important to accomplish greater precision and to reduce undesired outcomes such as off-target events. The use of small molecules to control CRISPR/Cas activity represents a promising direction. Here, we provide an updated review on multiple drug inducible CRISPR/Cas systems and discuss their distinct properties. We arbitrarily divided the emerging drug inducible CRISPR/Cas systems into two categories based on whether at transcription or protein level does chemical control occurs. The first category includes Tet-On/Off system and Cre-dependent system. The second category includes chemically induced proximity systems, intein splicing system, 4-Hydroxytamoxifen-Estrogen Receptor based nuclear localization systems, allosterically regulated Cas9 system, and destabilizing domain mediated protein degradation systems. Finally, the advantages and limitations of each system were summarized.
成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白(Cas)系统已成为一种强大的通用技术,用于可编程基因编辑、转录调控、表观遗传调控和基因组标记。然而,更好地控制其活性对于实现更高的精度和减少脱靶事件等不良后果至关重要。使用小分子来控制CRISPR/Cas活性是一个有前景的方向。在此,我们对多种药物诱导的CRISPR/Cas系统进行了更新综述,并讨论了它们的独特特性。基于化学控制是在转录水平还是蛋白质水平发生,我们将新兴的药物诱导CRISPR/Cas系统任意分为两类。第一类包括四环素调控系统(Tet-On/Off)和Cre依赖系统。第二类包括化学诱导邻近系统、内含肽剪接系统、基于4-羟基他莫昔芬-雌激素受体的核定位系统、变构调节的Cas9系统和去稳定结构域介导的蛋白质降解系统。最后,总结了每个系统的优缺点。