《生命科学》 2022, 34(10): 1207-1216

CRISPR筛选在生命医学研究中的应用

刘黎啸^1,2 , 荆耀彬^2,3,4,5 , 冀喆君^4,6 , 王　思^7,* , 曲　静^2,4,6,* , 张维绮^1,2,* , 刘光慧^2,3,4,5,*

¹中国科学院北京基因组研究所(国家生物信息中心)，中国科学院精准基因组医学重点实验室，北京 100101 ²中国科学院大学，北京 100049 ³中国科学院动物研究所膜生物学国家重点实验室，北京 100101 ⁴北京干细胞与再生医学研究院，北京 100101 ⁵中国科学院大学未来技术学院，北京 100190 ⁶中国科学院动物研究所干细胞与生殖生物学国家重点实验室，北京 100101 ⁷首都医科大学宣武医院国家老年疾病临床医学研究中心，人脑保护高精尖中心，北京 100053

摘　要：

CRISPR/Cas9 是一种高效、便捷的基因编辑工具，在生命科学领域具有广泛的应用。基于CRISPR/Cas9 系统构建基因组文库进行高通量筛选，有助于解析不同生物学背景下编码基因的功能和调控元件的特征。覆盖全基因组或特定生物途径的CRISPR 筛选支持在不同的遗传背景和时空环境下进行，有助于鉴定关键的生物学靶点，并阐述生理、病理条件下的基因功能及相互作用网络。本文总结了近年来CRISPR 筛选在衰老、肿瘤等疾病研究中的重要进展，概述了CRISPR 筛选与单细胞测序、功能基因组学等方法相结合的研究策略，并讨论了CRISPR 筛选面临的挑战以及可能的解决方案。

通讯作者：王　思 , Email:wangsi@xwh.ccmu.edu.cn 曲　静 , Email:qujing@ioz.ac.cn 张维绮 , Email:zhangwq@big.ac.cn 刘光慧 , Email:ghliu@ioz.ac.cn

Application of CRISPR screen in biomedical research

LIU Li-Xiao^1,2 , JING Yao-Bin^2,3,4,5 , JI Zhe-Jun^4,6 , WANG Si^7,* , QU Jing^2,4,6,* , ZHANG Wei-Qi^1,2,* , LIU Guang-Hui^2,3,4,5,*

¹CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China ²University of Chinese Academy of Sciences, Beijing 100049, China ³State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China ⁴Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China ⁵School of Future Technology, University of Chinese Academy of Sciences, Beijing 100190, China ⁶State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China ⁷Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China

Abstract:

CRISPR/Cas9 is an efficient and convenient gene-editing tool, which has been widely used in life science. The construction of a genome library based on CRISPR/Cas9 system for high-throughput screening can help to characterize the functions and regulatory elements of coding genes in different biological contexts. Genome-wide or specific biological pathways CRISPR screening supports experiments in different genetic and spatial-temporal settings. CRISPR screening can help identify key biological targets and explore the molecular, cellular, and systemic mechanisms underlying physiological and pathological conditions. Here, we review the important progress of CRISPR screening in the study of aging, tumor, and other diseases in recent years. We also outline the combined application of CRISPR screening with single-cell RNA sequencing, functional genomics, and other approaches. Finally, we discuss potential challenges for CRISPR screening and envision possible solutions.

Communication Author：WANG Si , Email:wangsi@xwh.ccmu.edu.cn QU Jing , Email:qujing@ioz.ac.cn ZHANG Wei-Qi , Email:zhangwq@big.ac.cn LIU Guang-Hui , Email:ghliu@ioz.ac.cn