CRISPR-Cas13a系统用于肿瘤诊断与治疗的进展

Advances of using CRISPR-Cas13a system for tumor diagnosis and treatment

摘要:

CRISPR-Cas系统是一种目前已知的基因编辑工具，其中以靶向DNA基因组编辑的CRISPR-Cas9系统的研究较为成熟。相较于靶向DNA的基因组编辑技术CRISPR-Cas9系统，近年来靶向RNA的Ⅵ型-CRISPR家族CRISPR-C2c2/Cas13a系统研究日渐增多。CRISPR-Cas13a系统具有特异性识别并结合单链RNA序列从而非特异性切割RNA的特点，可应用于检测肿瘤外周血游离核酸，对早期肿瘤患者进行筛查。同时，Cas13a在进行体内RNA切割的过程中，不涉及编码基因DNA的改变，可直接对基因转录产物mRNA进行编辑，达到基因修饰的目的，并能够同时靶向多基因转录产物从而调控基因的表达。Cas13a系统可应用于分子诊断及RNA编辑中，该系统在肿瘤的诊断与治疗中也被证实具有广阔的发展前景。基于已有的文献资料，文中综述了靶向RNA的CRISPR-Cas13a技术应用于肿瘤诊断与治疗的研究进展，探讨了CRISPR-Cas13a系统对癌症治疗的新思路及存在的局限，并展望了未来可能的研究方向。

Abstract:

CRISPR-Cas systems are well known gene editing tools, among which CRISPR-Cas9 system targeting DNA is the most well developed. Compared with CRISPR-Cas9 system, CRISPR-C2c2/Cas13a system derived from TYPE VI of CRISPR family that can target RNA has attracted increasingly intense investigations in recent years. The CRISPR-Cas13a system is featured by specific recognition and binding of single stranded RNA sequences, thus playing a role in non-specific cleavage of RNA. This feature could be potentially applied to detect free nucleic acid in tumors or peripheral blood as a diagnostic approach. Since Cas13a specifically targets RNA, it can directly edit mRNA transcripts of genomic DNA to achieve the downregulation of target proteins without involving DNA editing. Therefore, Cas13a system could be used in tumor treatment. This review summarized the advances of using CRISPR-Cas13a for RNA targeting in tumor diagnosis and treatment, and prospected future applications.