基因组的“读-改-写”技术

doi:10.12211/2096-8280.2020-013

合成生物学 ›› 2020, Vol. 1 ›› Issue (5): 503-515.doi: 10.12211/2096-8280.2020-013

基因组的“读-改-写”技术

王会^1,², 戴俊彪^1,², 罗周卿²

^1.深圳大学生命与海洋科学学院，广东深圳 518055
^2.中国科学院深圳先进技术研究院，深圳合成生物学创新研究院，合成基因组学研究中心，广东省合成基因组学重点实验室，深圳合成基因组学重点实验室，广东深圳 518055

收稿日期:2020-02-29 修回日期:2020-04-19 出版日期:2020-10-31 发布日期:2020-12-03
通讯作者: 戴俊彪,罗周卿
作者简介:王会(1993—)，女，硕士研究生，主要研究方向为合成生物学。E-mail：15225377578@163.com|戴俊彪（1974—），男，博士，研究员，主要研究方向为合成生物学。E-mail：junbiao.dai@siat.ac.cn|罗周卿（1990—），男，博士，副研究员，主要研究方向为合成生物学。E-mail：zq.luo@siat.ac.cn
基金资助:
国家重点研发计划“合成生物学”重点专项(2018YFA0900100);国家自然科学基金(31725002);深圳合成基因组学重点实验室项目(ZDSYS201802061806209);广东省合成基因组学重点实验室(2019B030301006);深圳市科技计划(KQTD20180413181837372)

Reading, editing, and writing techniques for genome research

Hui WANG^1,², Junbiao DAI^1,², Zhouqing LUO²

^1.College of Life Sciences and Oceanography，Shenzhen University，Shenzhen 518055，Guangdong，China
^2.Guangdong Provincial Key Laboratory of Synthetic Genomics，Shenzhen Key Laboratory of Synthetic Genomics，Center for Synthetic Genomics，Shenzhen Institute of Synthetic Biology，Shenzhen Institutes of Advanced Technology，Chinese Academy of Sciences，Shenzhen 518055，Guangdong，China

Received:2020-02-29 Revised:2020-04-19 Online:2020-10-31 Published:2020-12-03
Contact: Junbiao DAI,Zhouqing LUO

摘要/Abstract

摘要：

基因组是生命系统的指令中枢，对基因组的研究是生命科学的核心内容，基因组研究相关技术的开发是深化对基因组序列和功能认识的重要推动力量。通过基因组测序获取基因组全序列，通过人工诱变、定点编辑研究基因组局部序列的功能与调控，通过对基因组的从头设计与化学再造实现对生命性状的定制，是基因组研究的三个不同层面。从一代测序到三代测序，基因组“读”技术极大地降低了成本和难度，提升了速度和精准度，引领着复杂基因组、大型基因组从草图走向完成图时代。通过人工诱变、定点编辑等技术可以改变野生型基因组的局部序列，研究基因组序列的功能与调控。从人工诱变到定点编辑，从ZFN到CRISPR，基因组“改”技术在效率、适用对象和简便性上有了显著的提高，为“基因型-表型”研究提供了有力工具，精准编辑、高通量编辑逐步走向应用。通过对基因组的从头设计与化学再造，书写人工基因组，可以获得对基因组全局的系统认识，实现对生命性状的定制。从病毒基因组合成、细菌基因组合成到酵母基因组合成，再到国际基因组写计划，基因组“写”技术在适用对象上不断拓展，人工设计、化学再造正成为复杂生物学问题研究和已有性状优化、新性状引入的一把利器。本文主要综述了基因组测序（读）、基因组编辑（改）和基因组合成（写）技术的发展历程、各自的特征、目前的研究进展及在基因组研究方面的一些应用，并对近期相关技术的可能突破点进行了总结和展望。“读-改-写”技术互为支撑，推动基因组研究在致知和致用领域两面开花。

关键词: 合成生物学, 功能基因组, 基因组测序, 基因组编辑, 合成基因组学

Abstract:

Genome carries the entire genetic information of life. Genome-related researches are ultimate fundamentals for life sciences. Technological development in genomic researches has deepened our understanding of genomes and their function. Obtaining genome sequences through sequencing, studying their function and regulation through editing and creating customer designed genomes through synthesis are three important aspects of genome research. From the first-generation sequencing to the third-generation sequencing, the "reading" technology has greatly reduced the cost and difficulty, while improved the speed, enabling the production of complete genomic information for complex and large genomes. From random mutagenesis to site-specific genome editing and, from ZFN to CRISPR, the genome "editing" technology has improved significantly in efficiency, applicability, and simplicity, providing a wealth of materials to dissect "genotype-phenotype" relationship. Accurate editing and high-throughput editing are moving towards applications in various areas. From viral genome, bacterial genome to yeast genome, and ultimately to human genome, synthetic genomics has moved from simple organisms to many complex organisms. Precise, fast and low-cost synthesis technologies are important for the development of synthetic genomics. This article reviews the histories, features, present status, and applications of technologies for genome sequencing (reading), genome editing (editing) and genome synthesizing (writing). The potential breakthrough of these technologies in the near future is also summarized and prospected. The ability to read, edit and write a genome has been and will continue to advance not only our understanding but also better utilization of living systems.

Key words: synthetic biology, functional genomics, genome sequencing, genome editing, synthetic genomics

中图分类号:

王会, 戴俊彪, 罗周卿. 基因组的“读-改-写”技术[J]. 合成生物学, 2020, 1(5): 503-515, doi: 10.12211/2096-8280.2020-013.

Hui WANG, Junbiao DAI, Zhouqing LUO. Reading, editing, and writing techniques for genome research[J]. Synthetic Biology Journal, 2020, 1(5): 503-515, doi: 10.12211/2096-8280.2020-013.

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基因组的“读-改-写”技术

Reading, editing, and writing techniques for genome research

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