CRISPR-Cas9研究进展及在基因治疗上的应用

CRISPR-Cas9Clustered regularly interspaced short palindromic repeats（CRISPR）/CRISPR-associated （Cas）9]是近年兴起的一种高特异性和高效的基因编辑新技术，由向导RNA（single guide RNA，sgRNA）和cas9（CRISPR-associated 9）蛋白组成，引起DNA位点特异性双链断裂（double-strand breaks，DSBs），引发同源重组修复（homology-directed repair，HDR）或非同源末端连接修复（non-homologous end joining，NHEJ），达到靶基因修饰的作用。CRISPR-Cas9技术自发现以来，因其便于操作、花费较低、高特异性、可同时打靶任意数量基因等优点而被应用。近年研究显示，对于一些遗传性疾病，可通过CRISPR-Cas9精确的基因编辑破坏致病的内源基因、改正引起疾病的突变体或插入新的保护性基因进行治疗，该技术为基因治疗开启了一个新方向。主要从CRISPR-Cas9结构、作用机制及在疾病基因治疗上的应用等方面进行了综述。

Research Progress of CRISPR-Cas9 and Its Application in Gene Therapy

CRISPR-Cas9 is a novel highly specific and efficient technology of genome editing. CRISPR-Cas9 system consists of single guide RNA (sgRNA) and Cas9 protein, it can produce site-specific DNA double-strand breaks (DSBs), then induces the repair of nonhomologous end-joining (NHEJ) or homology-directed repair (HDR) that gives rise to targeted genome modifications. Since its discovery, with its several advantages of easy operation, low cost, high efficiency and simultaneous targeting of arbitrary number of gene and so on, it has been widely applied. Recent researches show that the genome editing of CRISPR-Cas9 provides a new direction for gene therapy, through accurate disruption of causative endogenous gene or correction of the causative mutation or insertion of a new protective gene.The structure and the mechanism of CRISPR-Cas9, and also its gene therapy in diseases were reviewed and highlighted.