合成生物学 ›› 2025, Vol. 6 ›› Issue (4): 764-788.DOI: 10.12211/2096-8280.2025-048

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非生物元件增强的合成生物杂合体系研究进展

黄瑜晴1, 吴涵1, 李晓彬1, 刘君禹1, 马少华1,2, 戈钧2,3, 邢新会1,2,3, 张灿阳1,2   

  1. 1.清华大学深圳国际研究生院生物医药与健康工程研究院,广东 深圳 518005
    2.工业生物催化教育部重点实验室(清华大学),北京 100084
    3.清华大学化学工程系,北京 100084
  • 收稿日期:2025-05-23 修回日期:2025-07-13 出版日期:2025-08-31 发布日期:2025-09-03
  • 通讯作者: 张灿阳
  • 作者简介:黄瑜晴(2001—),女,硕士研究生。研究方向为口服递送大分子-工程菌杂合体系设计与创制。E-mail:huangyq23@mails.tsinghua.edu.cn
    吴涵(2000—),男,硕士研究生。研究方向为中性粒细胞介导的PAE纳米颗粒靶向药物递送体系设计与开发。E-mail:wuhan23@mails.tsinghua.edu.cn
    张灿阳(1985—),男,副教授,博士生导师。研究方向为面向生物医药与生命健康领域重大需求与问题,设计和开发多功能工程化生物材料载体和递送(剂型)策略,用于疾病诊断与治疗,如癌症、感染、自身免疫性疾病,具体包括:刺激-响应型(聚β-氨基酯)材料库的设计(计算机辅助和模拟)与建立;细胞介导的免疫调控靶向系统的开发;基于产品工程与制剂工程的生物医药与健康工程研究;微针相关技术与产品开发。 E-mail:zhang.cy@sz.tsinghua.edu.cn
    第一联系人:共同第一作者
  • 基金资助:
    国家重点研发计划(2023YFA0913600);国家重点研发计划(2023YFA0913602)

Recent advancements in non-biological component-augmented synthetic bio-hybrid systems

HUANG Yuqing1, WU Han1, LI Xiaobin1, LIU Junyu1, MA Shaohua1,2, GE Jun2,3, XING Xinhui1,2,3, ZHANG Canyang1,2   

  1. 1.Institute of Biopharmaceutical and Health Engineering,Tsinghua Shenzhen International Graduate School,Shenzhen 518005,Guangdong,China
    2.Key Laboratory of Industrial Biocatalysis,Ministry of Education,Tsinghua University,Beijing 100084,China
    3.Department of Chemical Engineering,Tsinghua University,Beijing 100084,China
  • Received:2025-05-23 Revised:2025-07-13 Online:2025-08-31 Published:2025-09-03
  • Contact: ZHANG Canyang

摘要:

利用人工非生物元件对生命体进行设计与改造是合成生物学的一大机遇。开发非生物元件-生物元件合成生物杂合体系,可以突破天然生化反应的局限,实现生物元件与非生物元件的协同增效和功能超越,在生物制造和生物医药新应用领域前景广阔,已成为合成生物学研究中备受关注的前沿方向。然而,相比于类型繁多和功能丰富的非生物元件,现有杂合体系的功能还较为单一。针对这一问题,本文系统综述了近年来非生物元件-生物元件合成生物杂合体系的研究进展,依据体系类型进行分类总结,通过对典型研究的深入分析,在归纳其功能实现途径的基础上,进一步揭示了现有体系在功能扩展和机制解析方面的局限性,并展望了该领域在多平台联用、工程化设计和精准调控等方面的发展前景。

关键词: 非生物元件, 合成生物杂合体系, 协同增效, 生物制造, 生物医药

Abstract:

The integration of non-biological components into living systems represents a pivotal advance in synthetic biology. This approach facilitates the creation of synthetic bio-hybrid systems effectively overcoming inherent limitations of natural biological systems. By leveraging the synergistic enhancement and superior functionalities derived from both biological and non-biological constituents, these hybrid systems exhibit immense potential across diverse applications, including bio-manufacturing, precise diagnostics, and biomedicine, establishing them as a cutting-edge frontier. However, despite the vast functional diversity of non-biological components, current bio-hybrid systems often present functional singularity, and their underlying synergistic mechanisms remain insufficiently elucidated. These limitations hinder their broader adoption and sophisticated applications. To address these challenges, this review systematically summarizes recent advancements in non-biological component-enhanced synthetic bio-hybrid systems. We categorize these systems based on the nature of the non-biological components (e.g., nanomaterials, polymers, semiconductors) and their integration strategies with diverse biological entities (e.g., enzymes, nucleic acids, cells). Through in-depth analysis of representative studies, we elucidate construction methodologies, functional realization pathways, and performance characteristics across various hybrid configurations. A central focus is to critically identify existing limitations, particularly concerning functional modularity, fine-tuned control, and the comprehensive elucidation of complex underlying mechanisms. We also explore strategies to overcome these challenges, emphasizing rational design and advanced characterization. Looking ahead, we present a forward-looking perspective on the future trajectory of this burgeoning field. Key areas for advancement include multi-platform integration, combining various non-biological components with multiple biological parts for highly sophisticated systems. Furthermore, we highlight the importance of advanced engineering design and high-throughput screening to accelerate discovery and optimization. The refinement of precise spatiotemporal regulation is crucial for controlling complex assemblies. Moreover, the integration of artificial intelligence and machine learning for rational design promises to revolutionize development. This review aims to serve as a valuable resource, providing critical insights and inspiring further research into the design, construction, and application of non-biological component-enhanced synthetic bio-hybrid systems, therefore paving the way for groundbreaking innovations in healthcare and biotechnology. {L-End}

Key words: non-biopart, synthetic biological hybrid systems, synergistic enhancement, biomanufacturing, biopharmaceutics

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