哺乳动物合成基因组学研究进展

何博; 付宗恒; 吴毅; 赵广荣

doi:10.12211/2096-8280.2021-006

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哺乳动物合成基因组学研究进展

特约评述 | 更新时间：2025-03-20

- 哺乳动物合成基因组学研究进展
- Research progress of synthetic mammalian genomics
- 合成生物学 2022年3卷第1期页码：78-97
- 作者机构：
  
  天津大学化工学院，系统生物工程教育部重点实验室，教育部合成生物学前沿科学中心，天津 300072
- 作者简介：
  
  [ "何博（1995—），女，博士研究生。研究方向为合成基因组学。E-mail：hebo@tju.edu.cn" ]
  [ "吴毅（1989—），男，博士，研究员，博士生导师。研究方向为合成基因组学。E-mail：yi.wu@tju.edu.cn" ]
  [ "赵广荣（1966—），男，博士，教授，博士生导师。研究方向为合成生物学。E-mail：grzhao@tju.edu.cn" ]
- 基金信息：
  
  国家重点研发计划“合成生物学”重点专项(2019YFA0903800)
- DOI：10.12211/2096-8280.2021-006
  中图分类号： Q81
- 收稿：2021-01-13，
  
  修回：2021-11-27，
  
  纸质出版：2022-02-28
- 稿件说明：
移动端阅览
何博，付宗恒，吴毅，赵广荣. 哺乳动物合成基因组学研究进展［J］. 合成生物学， 2022， 3（1）： 78-97

HE Bo， FU Zongheng， WU Yi， ZHAO Guangrong. Research progress of synthetic mammalian genomics［J］. Synthetic Biology Journal， 2022， 3（1）： 78-97
何博，付宗恒，吴毅，赵广荣. 哺乳动物合成基因组学研究进展［J］. 合成生物学， 2022， 3（1）： 78-97 DOI： 10.12211/2096-8280.2021-006.

HE Bo， FU Zongheng， WU Yi， ZHAO Guangrong. Research progress of synthetic mammalian genomics［J］. Synthetic Biology Journal， 2022， 3（1）： 78-97 DOI： 10.12211/2096-8280.2021-006.

摘要

合成基因组学通过设计与合成大片段DNA序列，开展基因组尺度的工程化改造或从头合成，从而揭示基因型和表型的关联，并构建预定功能的生物。正如在大肠杆菌、酿酒酵母等低等模式生物中合成基因组学的实践，对哺乳动物基因组的大片段DNA设计再造也必然会加深对更为复杂的动物基因组的理解并加强对基因组的功能重塑。面对生命健康领域存在的重大挑战，设计合成哺乳动物大片段DNA为其提供了新的思路和解决方案，特别是在染色体疾病模型构建、人源化免疫系统等方面展示出独特的应用潜力。然而，目前大片段DNA在哺乳动物细胞中的设计和操纵仍是一个巨大的挑战，面临着高等哺乳动物基因组注释不完善、复杂序列组装困难、穿梭载体通用性差、大片段DNA转移低效等问题。本文围绕设计-组装-转移的技术路线，评述哺乳动物合成基因组学领域的重要研究进展，详细介绍重要的技术突破，并展望哺乳动物合成基因组学在医药健康领域的应用。

Abstract

Synthetic genomics aims at genome-scale engineering or

de novo

synthesis through the design and chemical synthesis of large DNA sequences

which contributes to the revealing of connections between genotype and phenotype to construct organisms with expected functions. With the advances of synthetic genomics in lower model organisms

such as

Escherichia coli

and

Saccharomyces cerevisiae

designing and rebuilding the large DNA fragments for mammalians could enhance the functional remodeling of their genomes. Designing higher mammalian genomes based on principles developed with the lower organism genome design can lead to understanding of more complex mammalian genomes

and in the meantime improve th

e design principles. In spite of multiple challenges

design and synthesis of mammalian large DNA fragments would provide promising methods and solutions. Overcoming the technical difficulties of manipulating large fragments of DNA in mammalian cells shows unique potentials in a variety of applications. For example

it can customize chromosomes for the construction of chromosomal disease models

build more complete humanized immune systems

etc. However

the current design and manipulation of large DNA fragments in mammalian cells are faced with many unsolved bottlenecks. Although the whole genome sequencing of several higher mammals has been completed

the annotation for the genomes of higher mammals is still far from complete. The existing assembly technology is difficult to accurately assemble complex repetitive sequences

and the vector presents poor versatility for shuttling between different cells. Moreover

the lower efficiency in transferring large fragments of DNA is a major bottleneck hindering the manipulation of large fragments in mammalian cells. This article systematically reviews recent progress in synthetic mammalian genomics by focusing on the breakthroughs in design-assembly-transfer technical route

and highlights further applications in human medicines and healthcare field.

关键词

Keywords

references

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