CRISPR-dCas9转录调控系统及其在遗传病治疗研究中的应用  

The CRISPR-dCas9 system regulating genomic transcription and its application in genetic disease therapy

作　　者：李博文 梁世倩 白健 秦鸿雁 LI Bo-Wen;LIANG Shi-Qian;BAI Jian;QIN Hong-Yan(2015 Biological Technology Major, School of Pharmacy, The Fourth Military Medical University,Xi'an 710032, China;Department of Medical Genetics and Developmental Biology,The Fourth Military Medical University, Xi’an 710032, China)

机构地区：[1]空军军医大学药学系,西安710032 [2]空军军医大学基础医学院医学遗传与发育生物学教研室,西安710032

出　　处：《生命科学》2019年第6期628-636,共9页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金重点项目(81530018);肿瘤生物学国家重点实验室青年自主课题(CBSKL-2017Z13)

摘　　要：CRISPR-Cas9是一种强大的基因组编辑系统,随着研究的深入,科学家建立了调控基因组转录的CRISPR-dCas9系统。该系统的建立基于dCas9的发现,dCas9丧失核酸酶活性,虽不具有DNA切割活性,但仍然具有DNA结合活性,其可在sgRNA的引导下靶向目的基因,将特定的转录激活因子(或抑制因子)携带至目的基因上游,实现对目的基因的转录激活(CRISPRa)或转录抑制(CRISPRi)。目前该系统已用于遗传病治疗的实验研究,取得了可喜的进展,具有潜在的临床应用价值。该文从CRISPR-dCas9系统建立、发展以及在几种遗传病治疗领域的研究进行了综述。The bacterial CRISPR-Cas system is one powerful genome editing system guided by a single guide RNA(sgRNA). Recently, using an engineered nuclease-deficient Cas9, termed dCas9, one new CRISPR-dCas9 system is established, which can target genomic DNA without cleaving. In detail, dCas9, carrying a specific transcriptional activator(or inhibitor) to upstream of the target gene, can regulate specific gene expression including repression through CRISPR interference(CRISPRi) and activation through CRISPR activation(CRISPRa). The CRISPRdCas9 system has been applied in studies of genetic disease therapy, which have the potential clinic application value. In this review, we elucidate the development of CRISPR-dCas9 system and its application in several genetic disease therapy, such as Duchenne muscular dystrophy, fragile X syndrome and retinitis pigmentosa.

关 键 词：死亡Cas9 CRISPR激活 CRISPR抑制 杜氏肌营养不良 脆性X染色体综合征 色素性视网膜炎 

分 类 号：Q-7[生物学]