《生命科学》 2018, 30(9): 916-925

CRISPR/Cas9系统应用于早期胚胎编辑和基因治疗

张晓宇1，2，唐　蔚1，李劲松1，2*

(1 中国科学院生物化学与细胞生物学研究所，分子细胞卓越中心，上海 200031；
    2 细胞生物学国家重点实验室，上海 200031)

摘　要：摘　要：CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) 系 统具有高效、精确、操作难度较低等特点，是目前应用最为广泛的基因编辑工具。CRISPR/Cas9 在构建模式动物突变体研究基因功能和构建人类疾病模型中有大量使用，但是由于相关伦理限制，在人类胚胎中进行基因编辑来探索治疗性胚胎编辑和研究人早期胚胎发育机制的研究发展较慢。人类胚胎发育机制与小鼠等模式动物的早期胚胎发育机制存在较大差异，过往在模式动物上研究的早期胚胎发育机制要在人类胚胎水平进行验证，对人类胚胎利用基因编辑工具进行直接研究越发必要，探索人类早期胚胎发育机制有助于相关发育疾病的研究与治疗。胚胎治疗性基因编辑可以实现对遗传疾病的彻底阻断，目前还处于初步探索时期，但是主要存在潜在脱靶和编辑后形成嵌合体两方面问题。相较而言，出生后个体水平的基因治疗目前发展较为快速，对遗传疾病和艾滋病等血液疾病有应用价值。现对CRISPR/Cas9 近年来应用于人类胚胎编辑和基因治疗的内容进行了综述。

CRISPR/Cas9 system in early-stage embryo genome editing and gene therapy

ZHANG Xiao-Yu1，2， TANG Wei1， LI Jin-Song1，2*

(1 CAS Center for Excellence in Molecular Cell Science， Shanghai Institute of Biochemistry and Cell Biology， Chinese Academy of Sciences， Shanghai 200031， China; 2 State Key Laboratory of Cell Biology， Shanghai 200031， China)

Abstract: Abstract: CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) system is the most widely used genome editing tool in recently several years， standing out as an efficient and precise method which is easy to handle. CRISPR/Cas9 promotes the generation of genetic mutation animal models and human disease models. Because of ethical problem， genome editing in human embryo is strictly restricted. Human early-stage embryo development mechanism has a mount of differences compared with mouse and other model organisms， so the previous findings need to be verified in human and the need to study human embryo directly is rising， which will promote learning and curing the developmental diseases. Genome editing can fundamentally block heritage diseases， through facing two major issues， off-target and mosaic. Compared with therapeutic human embryo genome editing， at this stage， gene therapy on postnatal stage progresses more rapidly aiming at curing genetic disease and hematologic diseases such as AIDS (Acquired Immune Deficiency Syndrome). This review focus on the human embryo genome editing and gene therapy achievement in the past three years.