合成基因线路的工程化设计研究进展与展望

高歌; 边旗; 王宝俊

doi:10.12211/2096-8280.2023-096

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合成基因线路的工程化设计研究进展与展望

特约评述 | 更新时间：2025-06-20

- 合成基因线路的工程化设计研究进展与展望
- Synthetic genetic circuit engineering: principles, advances and prospects
- 合成生物学 2025年6卷第1期页码：45-64
- 作者机构：
  
  1.浙江大学化学工程与生物工程学院，浙江杭州 310058
  2.浙江大学杭州国际科创中心，浙江杭州 311200
- 作者简介：
  
  [ "高歌（1994—），女，博士，助理研究员。研究方向为合成生物学基因线路设计、肿瘤细菌疗法。 E-mail：gaoge@zju.edu.cn" ]
  [ "边旗（1993—），女，博士，助理研究员。研究方向为合成生物学使能技术开发、代谢工程。 E-mail：bianqi@zju.edu.cn" ]
  [ "王宝俊（1982—），男，浙江大学求是讲席教授，教育部长江学者讲席教授。研究方向为合成生物学和生物工程，长期从事合成生物使能技术、基因线路设计研究及其在生物传感、智能治疗和生物制造等领域的创新应用。 E-mail：baojun.wang@zju.edu.cn" ]
- 基金信息：
  
  国家重点研发计划“合成生物学”重点专项(2023YFF1204500);浙江省“尖兵”“领雁”研发攻关计划项目(2024C03011);国家自然科学基金重点国际合作研究项目(32320103001);国家自然科学基金面上项目(32271475);中央高校基本科研业务费专项资金(226-2022-00214)
- DOI：10.12211/2096-8280.2023-096
  中图分类号： Q81
- 收稿：2023-12-01，
  
  修回：2024-04-10，
  
  纸质出版：2025-01-31
- 稿件说明：
移动端阅览
高歌，边旗，王宝俊. 合成基因线路的工程化设计研究进展与展望［J］. 合成生物学， 2025， 6（1）： 45-64

GAO Ge， BIAN Qi， WANG Baojun. Synthetic genetic circuit engineering： principles， advances and prospects［J］. Synthetic Biology Journal， 2025， 6（1）： 45-64
高歌，边旗，王宝俊. 合成基因线路的工程化设计研究进展与展望［J］. 合成生物学， 2025， 6（1）： 45-64 DOI： 10.12211/2096-8280.2023-096.

GAO Ge， BIAN Qi， WANG Baojun. Synthetic genetic circuit engineering： principles， advances and prospects［J］. Synthetic Biology Journal， 2025， 6（1）： 45-64 DOI： 10.12211/2096-8280.2023-096.

摘要

合成基因线路利用合成生物学的技术和方法，将生物元件进行重新设计与构建，使人工设计的生物分子线路在活细胞中行使特定生物功能，在生物制造、医疗健康以及环境监测等领域具有巨大的潜力。但其工程化设计仍受到各种因素的制约，包括正交元器件数量有限、大规模线路组装困难、线路行为预测性低等。根据研究者们开发的各种调控元件工具箱和组装方法，本文逐点阐述了工程化设计基因线路所需遵循的几个核心原则：正交化、标准化、模块化与自动化。文章从DNA复制、转录和翻译层面介绍了正交基因元件库的构建和改造方法；全面总结了基因元件的标准化定量表征方法与标准元件设计方法；并介绍了本团队与其他团队在模块化基因线路设计方面的相关进展；分别从软件、硬件和人工智能角度展示如何实现基因线路的自动化设计。最后，本文探讨了基因线路设计的未来发展趋势，指出需要进一步融合人工智能和自动化等信息技术来加速基因线路“设计-构建-测试-学习”循环的迭代，提高线路设计的功能可预测性和复杂性，高效设计出符合目标需求的人造生命体。

Abstract

Synthetic genetic circuits are engineered gene networks comprised of redesigned genetic parts for interacting to perform customized functions in cells. With the rapid development of synthetic biology

synthetic genetic circuits have shown significant application potentials in many fields such as biomanufacturing

healthcare and environmental monitoring

. However

the efforts to scale up genetic circuits are hindered by the limited number of orthogonal parts

the difficulty of functionally composing large-scale circuits

and the poor predictability of circuit behaviors. A longstanding goal of synthetic biology research is to engineer complex synthetic biological circuits

using modular genetic parts

as we do with electronic circuits. Synthetic biologists have developed various genetic toolboxes and functional assembly methods over the past few decades. Here we present an overview of the latest advances

challenges

and future prospects in genetic circuit engineering from four aspects corresponding to the four key engineering principles for circuit design

i.e

. orthogonality

standardization

modularity

and automation. Firstly

the design and construction of orthogonal genetic part libraries are discussed in both prokaryotes and eukaryotes at the levels of DNA replication

transcription

and translation

respectively. Standardized characterization methods and the design of modular genetic parts are subsequently summarized. Furthermore

progress in developing modular genetic circuits are presented

providing new concepts and ways for engineering increasingly large and complex circuits. Finally

how to achieve automated design and building of genetic circuits are addressed from the advances in software

hardware and artificial intelligence

respectively

with an aim to replacing the presently time-consuming manual trial-and-error mode with the iterative "design-build-test-learn" cycle for improved efficiency and predictability of circuit design. The integration of these fundamental principles and the latest advances in information technology such as artificial intelligence and lab automation will accelerate the paradigm shift in genetic circuit engineering and synthetic biology research

making it feasible for designing synthetic lives to meet various customized needs.

关键词

Keywords

references

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