规律成簇间隔短回文重复序列及其相关蛋白基因编辑技术在感染性疾病诊断中的应用及其进展

The application and progress of clustered regularly interspaced short palindromic repeats and associated proteins gene editing technology in the diagnosis of infectious diseases

规律成簇间隔短回文重复序列(CRISPR)与相关蛋白Cas(CRISPR-Cas)系统是近来的研究热点,除在基因编辑方面有重要作用外,其应用于感染性疾病诊断方面也有很好的发展前景。传统感染性疾病检测及分子检测诊断技术在操作、检测周期及敏感度、特异度等方面存在不足。随着对CRISPR-Cas系统的深入研究,针对其特异核酸的识别和遗传修饰功能,可开展对感染性病原体检测技术的应用,目前发现可应用于检测的主要有Cas9、Cas12a和Cas13核酸酶。利用该检测技术的高效性、特异性和可编程性,可开展对寨卡病毒、登革热病毒、疟疾菌株、结核分枝杆菌、人乳头瘤病毒、埃博拉病毒、乙型肝炎病毒及严重急性呼吸综合征冠状病毒2等一系列感染性疾病病原体的检测。CRISPR-Cas基因编辑技术可能成为一种快速、灵敏、特异、低廉和可靠的诊断技术,为感染性疾病的诊断提供重要的理论依据。笔者主要对Cas9、Cas12a、Cas13等在感染性疾病诊断中的应用及其进展进行综述。

The clustered regularly interspaced short palindromic repeats(CRISPR)and associated proteins(CRISPR-Cas)systems are the hot research topics recently.In addition to their important roles in gene editing,CRISPR-Cas has a good prospect in the diagnosis of infectious diseases.Traditional diagnostic techniques for infectious diseases and molecular detection are inadequate in terms of operation,detection cycle,sensitivity and specificity.With the in-depth study of the CRISPR-Cas systems,the application of detection technology for infectious pathogens can be carried out in view of its specific nucleic acid recognition and genetic modification functions.At present,Cas9,Cas12a and Cas13 nucleases have been found to be the main ones that can be used for detection.The technology with high efficiency,specificity and programmability can be used for the detection of Zika virus,dengue,malaria,mycobacterium tuberculosis,human papilloma virus,Ebola,hepatitis B virus and severe acute respiratory syndrome corona virus 2,and a series of infectious diseases pathogens,which could become a rapid,sensitive,specific,cheap and reliable diagnosis technology,and provide important theoretical basis for the diagnosis of infectious diseases.This paper mainly reviews the application and progress of Cas9,Cas12a and Cas13 in the diagnosis of infectious diseases.