基因组编辑技术及其在合成生物学中的应用

doi:10.12211/2096-8280.2020-047

合成生物学 ›› 2020, Vol. 1 ›› Issue (4): 413-426.DOI: 10.12211/2096-8280.2020-047

基因组编辑技术及其在合成生物学中的应用

曹中正^1,², 张心怡³, 徐艺源³, 周卓^3,^4,^5,⁶, 魏文胜^1,^3,^4,^5,⁶

^1.北大-清华生命科学联合中心，北京 100871
^2.北京大学前沿交叉学科研究院，北京 100871
^3.北京大学生命科学学院，北京 100871
^4.北京大学生物医学前沿创新中心，北京 100871
^5.北京未来基因诊断高精尖创新中心，北京 100871
^6.北京大学基因组编辑研究中心，北京 100871

收稿日期:2020-04-13 修回日期:2020-09-24 出版日期:2020-08-31 发布日期:2020-11-02
通讯作者: 魏文胜
作者简介:曹中正（1992—），男，博士研究生，专业方向为生物化学与分子生物学。E-mail：czz949290@aliyun.com|魏文胜（1969—），男，博士，教授，研究方向为基因组编辑与功能性基因组学。E-mail：wswei@pku.edu.cn
基金资助:
国家自然科学基金重点项目(31930016)

Genome editing technology and its applications in synthetic biology

Zhongzheng CAO^1,², Xinyi ZHANG³, Yiyuan XU³, Zhuo ZHOU^3,^4,^5,⁶, Wensheng WEI^1,^3,^4,^5,⁶

^1.PKU-Tsinghua Center for Life Sciences，Beijing 100871，China
^2.Academy for Advanced Interdisciplinary Studies，Peking University，Beijing 100871，China
^3.School of Life Science，Peking University，Beijing 100871，China
^4.Biomedical Pioneering Innovation Center，Peking University，Beijing 100871，China
^5.Beijing Advanced Innovation Center of Genomics，Beijing 100871，China
^6.Peking University Genome Editing Research Center，Beijing 100871，China

Received:2020-04-13 Revised:2020-09-24 Online:2020-08-31 Published:2020-11-02
Contact: Wensheng WEI

摘要/Abstract

摘要：

基因组编辑技术是一种能够定向修改基因组的强有力工具。近年来，CRISPR/Cas9系统因其易于构建、编辑效率高等优点逐渐成为应用最为广泛的基因组编辑工具。合成生物学作为一门整合了工程学思维以及生物学原理的新生交叉学科，在生物学、医学、化学、农业、能源和环境等领域发挥着重要的作用。合成生物学对于DNA等遗传物质的合成、组装和编辑等操作有着巨大的需求，因此基因组编辑技术在合成生物学中有着广泛的应用。本文综述了以ZFN和TALEN为代表的早期基因组编辑技术，以及新型CRISPR/Cas9基因组编辑技术的原理、发展、作用机制、系统优化、衍生技术以及应用。同时也介绍了基因组编辑技术在基因表达调控、微生物基因编辑和分子记录等合成生物学领域的应用，并展望了基因组编辑技术的前景以及在合成生物学领域的发展趋势。

关键词: 基因组编辑, CRISPR/Cas9, 合成生物学, 基因表达调控, 微生物基因编辑, 分子记录

Abstract:

A vast amount of genetic information has been garnered with the rapid development of sequencing technology over the past decades. To decipher this information, genome editing tools that could functionally perturb specific genomic sequences have been developed. By recognizing DNA sequence, ZFN and TALEN emerged early as primitive genome editing approaches. Recently, the CRISPR/Cas9 system has become the most widely used genome editing tool due to its convenience of assembly and high efficiency. As a novel interdisciplinary field, synthetic biology has been developed through integrating engineering principles and biological fundamentals with the help from biotechnology tools. With the aim of improving our ability to decode and reprogram biological systems, synthetic biology has a tremendous demand for DNA synthesis, assembly and editing. With genome editing tools, synthetic biology promises innovations in the fields of biology, medicine, chemistry, agriculture, energy, environment, etc. In this review, we briefly describe the early genome editing tools: ZFN and TALEN. Furthermore, we comprehensively introduce the discovery, principle, development, optimization, derivative tools and applications of CRISPR/Cas9 system. Especially, we review the applications of these genome editing tools in synthetic biology from three aspects. The first is the application of genome editing tools in transcriptional regulation, such as precise gene expression regulation in dynamic biological process; the second is the application in engineering microbial strains, such as boosting the yield of antibiotic drugs and discovering potential resource for active natural products by manipulating specific gene or synthetic pathway; the last is their application in molecular recording, such as various approaches to record occurrence of detected signal or dynamic transcriptional information and to complete lineage tracing in live cells. Finally, we discuss current challenages and potential improvements of genome editing tools and envisage the future development of genome editing technology in synthetic biology.

Key words: genome editing, CRISPR/Cas9, synthetic biology, gene expression regulation, gene editing, molecular recording

中图分类号:

曹中正, 张心怡, 徐艺源, 周卓, 魏文胜. 基因组编辑技术及其在合成生物学中的应用[J]. 合成生物学, 2020, 1(4): 413-426.

Zhongzheng CAO, Xinyi ZHANG, Yiyuan XU, Zhuo ZHOU, Wensheng WEI. Genome editing technology and its applications in synthetic biology[J]. Synthetic Biology Journal, 2020, 1(4): 413-426.

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基因组编辑技术及其在合成生物学中的应用

Genome editing technology and its applications in synthetic biology

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