哺乳动物染色体工程研究进展

朱骊宇; 赵玉龙; 李伟; 王立宾

doi:10.12211/2096-8280.2022-072

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哺乳动物染色体工程研究进展

特约评述 | 更新时间：2025-03-20

- 哺乳动物染色体工程研究进展
- Progress in mammalian chromosome engineering
- 合成生物学 2023年4卷第2期页码：394-406
- 作者机构：
  
  1.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
  2.中国科学院大学，北京 100049
  3.中国科学院干细胞与再生医学创新研究院，北京 100101
  4.北京干细胞与再生医学研究院，北京 100101
- 作者简介：
  
  [ "朱骊宇（1997—），女，博士研究生。研究方向为基因治疗AAV载体筛选，合成生物学和哺乳动物染色体工程。E-mail：zhuliyu0204@163.com" ]
  [ "李伟（1982—），男，研究员，博士生导师。研究方向为结合基因工程、细胞工程和合成生物学等手段建立新的基因工程技术和细胞/动物模型。E-mail：liwei@ioz.ac.cn" ]
  [ "王立宾（1986—），男，博士后。研究方向为哺乳动物染色体工程，印记基因功能研究和复杂疾病动物模型的制备技术开发。E-mail：wlbfmb@126.com" ]
- 基金信息：
  
  国家重点研发计划(2019YFA0903800)
- DOI：10.12211/2096-8280.2022-072
  中图分类号： Q81
- 收稿：2022-12-11，
  
  修回：2023-02-27，
  
  纸质出版：2023-04-30
- 稿件说明：
移动端阅览
朱骊宇，赵玉龙，李伟，王立宾. 哺乳动物染色体工程研究进展［J］. 合成生物学， 2023， 4（2）： 394-406

ZHU Liyu， ZHAO Yulong， LI Wei， WANG Libin. Progress in mammalian chromosome engineering［J］. Synthetic Biology Journal， 2023， 4（2）： 394-406
朱骊宇，赵玉龙，李伟，王立宾. 哺乳动物染色体工程研究进展［J］. 合成生物学， 2023， 4（2）： 394-406 DOI： 10.12211/2096-8280.2022-072.

ZHU Liyu， ZHAO Yulong， LI Wei， WANG Libin. Progress in mammalian chromosome engineering［J］. Synthetic Biology Journal， 2023， 4（2）： 394-406 DOI： 10.12211/2096-8280.2022-072.

摘要

哺乳动物染色体工程是指通过多种实验手段对哺乳动物的染色体进行编辑，从而可以构建疾病动物模型、制备人源化药物工厂、解析物种进化机制甚至于合成全新生命。近些年，天然染色体改造技术、染色体设计与合成技术及染色体大片段转移技术等哺乳动物染色体工程的核心技术迅速发展，并相互交叉融合。同时，胚胎干细胞被发展为一种新型的哺乳动物合成生物学的底盘细胞，极大地推动了哺乳动物染色体工程的发展，催生了一大批用于医药和进化研究的动物模型，包括模拟唐氏综合征的小鼠模型、产生人类单克隆抗体的工具小鼠以及用于研究染色体重组生物学效应的染色体连接小鼠等，也极大推动了基础研究和生物医药领域的发展。但是，因为缺乏对哺乳动物染色体和发育的全面认知，所以对哺乳动物染色体的操纵仍面临诸多挑战，不仅包括技术手段，也包括生物伦理及安全性等。本文将对以上三种哺乳动物染色体工程主要的技术方法及其在多方面的应用进展进行简要综述，同时对哺乳动物染色体工程的进一步应用与挑战进行展望。

Abstract

Mammalian chromosome engineering refers to its editing through various methods to create animal models for chromosome diseases

pharmaceutical factories of human proteins

dissection of mechanism underlying evolution

and even synthetic life. In recent years

some milestone technologies of mammalian chromosome engineering

such as natural chromosome modifications

chromosome design and synthesis

and chromosome large fragment transfer

have been developed and integrated with each other. At the same time

embryonic stem cells have also been developed as a new chassis for mammalian synthetic biology. Applications of embryonic stem cells to synthetic biology greatly promote the development of mammalian chromosome engineering

giving birth to a large number of animal models for studies on diseases and evolution

including mouse models for Down syndrome

mice producing human monoclonal antibodies

and chromosome-ligation mice to study the biological effects of chromosome recombination. However

the manipulations of mammalian chromosomes are still challenging due to the lack of comprehensive understanding on chromosome composition and mammalian development. In addition to technological challenges

there are issues with bioethics and bio-safety. In this review

we review main technologies and current applications of mammalian chromosome engineering

and we also highlight future applications and challenges of mammalian chromosome engineering.

关键词

Keywords

references

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