外泌体糖链编辑及其功能调控研究进展

李瑞莲; 王倬; 杜昱光

doi:10.12211/2096-8280.2026-028

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外泌体糖链编辑及其功能调控研究进展

特约评述 | 更新时间：2026-09-04

- 外泌体糖链编辑及其功能调控研究进展
- Research progress on exosome glycan editing and its functional regulation
- 合成生物学 2026年7卷第4期页码：930-948
- 作者机构：
  
  中国科学院过程工程研究所，生物药制备与递送全国重点实验室，北京 100190
- 作者简介：
  
  李瑞莲（1993—），女，博士。研究方向为真菌胞外囊泡在慢性疾病中的致病机制。E-mail：rlli@ipe.ac.cn
  杜昱光（1963—），男，研究员，博士生导师。研究方向为糖链合成生物学与营养糖工程研究，推动功能糖产品在农业、食品及医药领域产业化应用。E-mail：ygdu@ipe.ac.cn
- 基金信息：
- DOI：10.12211/2096-8280.2026-028
  中图分类号： Q81
- 收稿：2026-04-20，
  
  修回：2026-07-03，
  
  纸质出版：2026-08-31
- 稿件说明：
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李瑞莲，王倬，杜昱光. 外泌体糖链编辑及其功能调控研究进展［J］. 合成生物学， 2026， 7（4）： 930-948

LI Ruilian， WANG Zhuo， DU Yuguang. Research progress on exosome glycan editing and its functional regulation［J］. Synthetic Biology Journal， 2026， 7（4）： 930-948
李瑞莲，王倬，杜昱光. 外泌体糖链编辑及其功能调控研究进展［J］. 合成生物学， 2026， 7（4）： 930-948 DOI： 10.12211/2096-8280.2026-028.

LI Ruilian， WANG Zhuo， DU Yuguang. Research progress on exosome glycan editing and its functional regulation［J］. Synthetic Biology Journal， 2026， 7（4）： 930-948 DOI： 10.12211/2096-8280.2026-028.

摘要

外泌体是介导细胞间通信的关键胞外囊泡，其表面糖链构成的糖萼结构被誉为细胞间通信的“糖密码”，在靶向识别、细胞摄取、免疫调节及信号转导中发挥核心作用。然而，天然外泌体糖链的高度异质性导致其作为药物递送载体时面临靶向性不足、胞内递送效率低、体内易被清除等临床转化瓶颈。外泌体糖链编辑技术通过精准修饰或重构糖链结构，为突破上述难题提供了革命性手段，成为糖生物学与纳米医学交叉领域的研究前沿。本文系统综述了外泌体糖链的组成特征、分析技术进展与核心生物学功能，重点阐述了宿主细胞工程、体外直接修饰、合成生物学重构三大糖链编辑策略的技术原理与应用优势，深入解析了糖链编辑对外泌体靶向特异性、细胞内吞途径、免疫原性及货物装载的调控机制，总结了工程化糖链编辑外泌体在肿瘤、炎症性疾病、神经退行性疾病与代谢性疾病治疗中的应用前景。同时，本文指出该领域目前面临外泌体异质性难控、糖链编辑精度不足、规模化制备成本高、临床转化标准缺失等挑战。未来将通过基因编辑、微流控、AI辅助设计等多技术融合，发展微环境响应型智能糖链编辑，深化糖链-货物调控机制解析，加快行业标准与监管体系建设，最终推动外泌体糖链编辑技术在精准医疗、靶向药物递送与疾病诊疗中的产业化落地。

Abstract

Exosomes are 30-150 nm extracellular vesicles secreted by nearly all living cells

serving as essential carriers for intercellular communication. The glycocalyx on exosome surfaces

mainly composed of glycans from glycoproteins and glycolipids

acts as a critical “glycocode” that governs target recognition

cellular internalization

immune modulation

and signal transduction. However

the inherent high heterogeneity of native exosome glycans severely restricts their clinical translation

especially as drug delivery vehicles

due to insufficient targeting

low intracellular delivery efficiency

and rapid clearance by the immune system

in vivo

. Exosome glycan editing

an emerging interdisciplinary technology integrating glycobiology

synthetic biology

chemical biology

and nanotechnology

enables precise manipulation

modification

de novo

reconstruction of exosome glycan structures

offering a revolutionary strategy to optimize exosome performance and expand their therapeutic applications. This review systematically summarizes the compositional characteristics

advanced analytical techniques

and core biological functions of exosome glycans. It elaborates on three major glycan editing strategies: host cell engineering (

in vivo

editing)

in vitro

direct modification

and synthetic biology reconstitution

highlighting their technical principles

advantages

and recent breakthroughs. The review further dissects the regulatory mechanisms of edited glycans on exosome biological behaviors

including targeting specificity

endocytic pathways

immunogenicity

and cargo loading (

e.g

miRNAs). It also comprehensively pr

esents the application prospects of glycan-engineered exosomes in the treatment of tumors

inflammatory diseases

neurodegenerative disorders

and metabolic diseases. Nevertheless

the field still faces critical challenges

such as uncontrollable exosome heterogeneity

limited precision of glycan editing

high costs of large-scale preparation

and the lack of standardized quality control and regulatory systems for clinical translation. Future directions will focus on the integration of CRISPR gene editing

cell-free synthesis

microfluidics

and AI-assisted glycan design to develop microenvironment-responsive intelligent glycan editing

elucidate the molecular mechanisms of glycan-cargo crosstalk

establish unified industrial standards

and accelerate clinical translation. This review underscores that interdisciplinary convergence is essential for achieving precise programming of exosome glycan functions

ultimately significantly accelerating the development of exosome-based precision medicine and biotherapeutics.

关键词

Keywords

references

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