Synthetic biology empowers breakthroughs in addressing immunotherapy limitations

WANG Ziheng; LIU Ziyi; MA Yuqian; QIN Hongyan; ZHAO Junlong; ZHANG Xiangqian

doi:10.12211/2096-8280.2025-074

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Synthetic biology empowers breakthroughs in addressing immunotherapy limitations

Invited Review | 更新时间：2026-01-15

- Synthetic biology empowers breakthroughs in addressing immunotherapy limitations
- Synthetic Biology Journal Vol. 6, Issue 6, Pages: 1311-1331(2025)
- 作者机构：
  
  1.延安大学生命科学学院，陕西延安 716099
  2.中国人民解放军空军军医大学基础医学院医学遗传与发育生物学教研室，陕西西安 710032
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-074
  CLC： Q816
- Received：21 July 2025，
  
  Revised：2025-10-28，
  
  Published：31 December 2025
- 稿件说明：
移动端阅览
王子恒，刘子怡，马毓谦，秦鸿雁，赵俊龙，张向前. 合成生物学助力突破免疫治疗局限性［J］. 合成生物学， 2025， 6（6）： 1311-1331

WANG Ziheng， LIU Ziyi， MA Yuqian， QIN Hongyan， ZHAO Junlong， ZHANG Xiangqian. Synthetic biology empowers breakthroughs in addressing immunotherapy limitations［J］. Synthetic Biology Journal， 2025， 6（6）： 1311-1331
王子恒，刘子怡，马毓谦，秦鸿雁，赵俊龙，张向前. 合成生物学助力突破免疫治疗局限性［J］. 合成生物学， 2025， 6（6）： 1311-1331 DOI： 10.12211/2096-8280.2025-074.

WANG Ziheng， LIU Ziyi， MA Yuqian， QIN Hongyan， ZHAO Junlong， ZHANG Xiangqian. Synthetic biology empowers breakthroughs in addressing immunotherapy limitations［J］. Synthetic Biology Journal， 2025， 6（6）： 1311-1331 DOI： 10.12211/2096-8280.2025-074.

摘要

免疫治疗近年来在肿瘤、感染性疾病和自身免疫疾病等领域取得了突破性进展，但其临床应用仍面临信号识别特异性不足、免疫反应调控不精准及毒副作用显著等挑战。合成生物学作为一门新兴的工程化学科，通过模块化设计和基因回路编程，为免疫治疗的精准化改造提供了创新解决方案。本文系统综述了合成生物学在免疫治疗中的关键技术、应用案例及未来方向，旨在为免疫治疗的工程化设计提供理论依据和技术参考。在信号输入环节，工程化受体（如Syn-Notch、RASSL）通过逻辑门控设计（如“与”门）增强靶向性，减少脱靶效应；在信号处理环节，人工基因回路（如CHOMP、SPOC）将病理信号转化为治疗性输出，实现选择性杀伤或动态调控；在信号输出环节，反馈系统和振荡回路（如负反馈抑制T细胞过度活化）优化免疫反应强度与时长，提升安全性。此外，合成生物技术已成功应用于CAR-T、CAR-NK等细胞疗法，通过受体改造、回路重编程等手段，显著提高疗效并降低毒性。未来，随着基因编辑、动态调控等技术的进一步发展，合成生物学驱动的免疫治疗将推动精准医学的实现，为复杂疾病的治疗提供更高效、更安全的策略。

Abstract

Immunotherapy has transformed modern medicine by powerfully mobilizing the body's immune system to combat malignancies

infectious diseases

and autoimmune disorders. Despite remarkable clinical successes

current immunotherapeutic approaches face substantial limitations

including inadequate target

specificity

dysregulated immune activation

and severe systemic toxicities. These challenges stem from the inherent complexity of biological systems and the pleiotropic nature of immune responses. Synthetic biology emerges as a transformative paradigm to address these limitations through rational engineering of immune cells and circuits. This discipline applies engineering principles to biological systems

enabling the design of sophisticated genetic circuits that confer precise spatiotemporal control over immune functions. This review comprehensively examines current synthetic biology strategies in immunotherapy

highlighting their mechanistic basis

clinical applications

and future directions for advancing precision medicine. Key innovations include: (1) engineered receptor systems (

e.g

Syn-Notch

RASSL) that implement Boolean logic operations for enhanced target discrimination; (2) synthetic signaling cascades (

e.g

CHOMP

SPOC) that convert pathological signals into therapeutic outputs; and (3) feedback-regulated circuits that dynamically modulate immune effector functions. These technologies have been successfully implemented in chimeric antigen receptor (CAR)-based therapies

where they improve tumor specificity while mitigating cytokine release syndrome and other adverse effects. Notably

synthetic biology facilitates the development of “smart” immunotherapies capable of environmental sensing

decision-making

and self-regulation. For instance

conditionally activated CAR-T cells demonstrate improved safety profiles through drug-inducible control systems

while synthetic cytokine circuits enable precise immune modulation. Furthermore

the integration of computational modeling with high-throughput screening accelerates the optimization of these engineered systems. Looking forward

synthetic biology promises to bridge critical gaps in conventional immunotherapy by enabling: (1) personalized therapeutic regimens through patient-specific circuit design; (2) multi-input di

agnostic capabilities for complex disease microenvironments; and (3) robust safety mechanisms to prevent off-target effects.As the field advances

the convergence of genome editing

biomaterials science

and artificial intelligence will unlock even greater therapeutic potential for engineered immune cells.

关键词

Keywords

references

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Related Institution

School of Life Sciences， Yan’an University， Yan’an 716000， Shannxi

Department of Medical Genetics and Developmental Biology， School of Basic Medical Sciences， Fourth Military Medical University， Xi’an 710000， Shannxi

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University of Chinese Academy of Sciences

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