Biosafety strategies for engineered bacteria

GAN Mudan; ZUO Jingrui; CAO Youzhi

doi:10.12211/2096-8280.2025-010

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Biosafety strategies for engineered bacteria

Invited Review | 更新时间：2026-03-07

- Biosafety strategies for engineered bacteria
- Synthetic Biology Journal Vol. 7, Issue 1, Pages: 265-278(2026)
- 作者机构：
  
  苏州大学功能纳米与软物质研究院，江苏苏州 215123
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-010
  CLC： Q816
- Received：14 February 2025，
  
  Revised：2025-04-27，
  
  Published：28 February 2026
- 稿件说明：
移动端阅览
甘牡丹，左静蕊，曹友志. 工程细菌的生物安全防控策略［J］. 合成生物学， 2026， 7（1）： 265-278

GAN Mudan， ZUO Jingrui， CAO Youzhi. Biosafety strategies for engineered bacteria［J］. Synthetic Biology Journal， 2026， 7（1）： 265-278
甘牡丹，左静蕊，曹友志. 工程细菌的生物安全防控策略［J］. 合成生物学， 2026， 7（1）： 265-278 DOI： 10.12211/2096-8280.2025-010.

GAN Mudan， ZUO Jingrui， CAO Youzhi. Biosafety strategies for engineered bacteria［J］. Synthetic Biology Journal， 2026， 7（1）： 265-278 DOI： 10.12211/2096-8280.2025-010.

摘要

随着人工设计的基因元件和工程菌应用于医学诊断和疾病治疗领域的增加，由此产生的生物安全风险也越来越受到重视。本文回顾了合成生物学的生物安全防控策略，特别介绍了近几年医学诊疗工程菌的生物安全防控研究。工程菌的生物安全防控可以防止宿主菌和基因元件脱离病灶区域向环境泄漏。基于营养缺陷或自杀基因的调控系统广泛用于限制工程菌的逃逸，基因元件拆分和靶向降解策略则可以防止基因元件扩散到环境中被其他细胞利用。环境中的代谢物和基因片段可能转移进入工程菌，这是导致生物安全防控机制失效的重要因素。非天然核苷酸和非天然氨基酸等非天然复制翻译系统的正交性好，可以大幅减少环境和工程菌间的相互影响。综合不同合成生物学原理设计的多层生物安全防控系统对于未来解决生物安全问题具有极大潜力。

Abstract

With the rapid rise of synthetic genes and engineered bacteria in disease diagnosis and treatment

they pose a growing risk of biosafety. We review the biosafety strategies based on synthetic biology

and especially highlight recent studies on biocontainments with diagnosis or therapeutic bacteria. There are several goals of controlling biocontainments. One is to reduce the escape of engineered bacteria by limiting them within biological barriers. The second is to prevent synthetic genes transferring from engineered bacteria into other organisms. Auxotrophies and kill-switch are widely applied in controlling the biocontainment of engineered bacteria. Auxotrophic organisms with essential genes knockout rely on key metabolites that are supplemented for survival. Kill-switches are inducible toxic gene circuits

such as suicide switches and toxin-antitoxin systems. Once engineered bacteria leave from human bodies

the toxic genes are switched on to kill them. Genetic separation and DNA breaking are useful strategies to keep synthetic genes from spreading into environmental organisms. Essential genes and genes of interest can be distributed into multiple vectors or chromosomes

and each vector or chromosome depends on the others for replications. DNA breaking technologies like CRISPR or other DNA nucleases are used to digest chromosome or plasmid inside engineered bacteria

which regulate host survival and synthetic gene transferring. The feeding of unusual metabolites or engineering specific genes into engineered bacteria could lead to the spreading failure of the biocontaminants. Several unnatural nucleic acids have been developed for replication and transcription

and much more unnatural amino acids are deployed for protein translation. One advantage of these unnatural systems is the orthogonality

which prevent synthetic genes from transferring to natural organisms. The chemically synthesized unnatural nucleic acids and amino acids are not present in environments

so the synthetic auxotrophies can overcome the cross-feeding limitation of natural auxotrophies. Biosafety systems with multiple-layered designs based on different synthetic biological principles have potentials to solve the challenges in the future.

关键词

Keywords

references

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Institute of Synthetic Biology， Shenzhen Institutes of Advanced Technology， Chinese Academy of Sciences

Department of Information Resources Management， School of Economics and Management， University of Chinese Academy of Sciences

National Science Library （Chengdu）， Chinese Academy of Sciences

Department of Chemical Engineering， Massachusetts Institute of Technology

Key Laboratory for Potato Biology of Yunnan Province， The CAAS-YNNU-YINMORE Joint Academy of Potato Science， Yunnan Normal University

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