《生命科学》 2019, 31(6): 628-636

CRISPR-dCas9转录调控系统及其在遗传病治疗研究中的应用

李博文1，2，梁世倩2，白　健2，秦鸿雁2*

(1 空军军医大学药学系2015级生物技术专业，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)

摘　要：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 CRISPR-dCas9 system regulating genomic transcription and its application in genetic disease therapy

LI Bo-Wen1，2， LIANG Shi-Qian2， BAI Jian2， QIN Hong-Yan2*

(1 2015 Biological Technology Major， School of Pharmacy， The Fourth Military Medical University，Xi’an 710032， China; 2 Department of Medical Genetics and Developmental Biology， The Fourth Military Medical University， Xi’an 710032， China)

Abstract: Abstract: 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.