CRISPR-mediated DNA cleavage by the CSM complex

CRISPR系统是最近发现的一种存在于许多微生物中的抗病毒防御系统。CRISPR蛋白使用小RNA来检测和摧毁具有相似序列的入侵病毒。CRISPR在微生物中起到适应性免疫系统的作用，类似于人类的免疫系统。用于寻找和摧毁入侵者的机制可分为三大类，I、II和III。CRISPR类型II已被非常成功地用于在许多不同生物中针对特定基因的基因组工程应用，并显示出巨大的生物技术和医学潜力。人们对第三类系统的了解要少得多，但可以提供一种替代技术，以追求同样的应用目标。我们最近发表了第一个CSM(IIIA型)CRISPR复合体的详细描述，现在我们希望详细了解该复合体与RNA和靶DNA物种结合的机制，靶DNA如何降解，并了解复合体的结构与其功能的关系。这一发现将具有根本性的科学意义，并可能为特定基因靶向的新技术的开发提供依据。

The CRISPR system is a recently discovered antiviral defence system present in many microbes. CRISPR proteins use small RNA's to detect and destroy invading viruses with similar sequences. CRISPR functions as a adaptive immune system in microbes, analogous to the human immune system. The machinery used to seek out and destroy invaders can be classified into three major types, I, II and III. CRISPR type II has been used very successfully to target specific genes for genome engineering applications in many different organisms and shows great biotechnological and medical potential. The type III system is much less well understood but could provide an alternative technology to pursue the same applied aims. We have recently published the first detailed description of a CSM (type IIIA) CRISPR complex and we now wish to pursue a detailed understanding of the mechanism by which this complex binds RNA and target DNA species, how degradation of target DNA happens and to understand how the structure of the complex relates to its functions. The findings will be of fundamental scientific interest and may also allow the development of new technologies for specific gene targeting.