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Research Progress on Exosome Glycan Editing and Its Functional Regulation
| 更新时间：2026-07-23
|
Research Progress on Exosome Glycan Editing and Its Functional Regulation
- 外泌体糖链编辑及其功能调控研究进展
- Synthetic Biology Journal Pages: 1-19(2026)
- 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：
- 基金信息：
DOI：10.12211/2096-8280.2026-028
CLC：Received：20 April 2026，
Revised：2026-07-03，
Online First：23 July 2026，
- 稿件说明：
移动端阅览
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. 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. DOI： 10.12211/2096-8280.2026-028
Research Progress on Exosome Glycan Editing and Its Functional Regulation
摘要
外泌体是介导细胞间通讯的关键胞外囊泡，其表面糖链构成的糖萼结构被誉为细胞间通讯的“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，并展望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
or 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 presents 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 emphasizes that interdisciplinary convergence is indispensable for achieving precise programming of exosome glycan functions
which will greatly boost the development of exosome-based precision medicine and biotherapeutics.
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关键词
Keywords
references
KALLURI R , LEBLEU V S . The biology, function, and biomedical applications of exosomes [J ] . Science , 2020 , 367 ( 6478 ).
王小蕾 , 郝嘉乐 , 傅庚辰 , 等 . 外泌体糖组学在生物医药领域的应用研究进展 [J ] . 药学进展 , 2024 , 48 ( 06 ): 450 - 462 .
WANG X L , HAO J L , FU G C , et al . Progress of research on the application of exosomal glycomics in biomedicine [J ] . Prog Pharm Sci , 2024 , 48 ( 06 ): 450 - 462 .
SHIMODA A , SAWADA S I , SASAKI Y , et al . Exosome surface glycans reflect osteogenic differentiation of mesenchymal stem cells: profiling by an evanescent field fluorescence-assisted lectin array system [J ] . Sci Rep , 2019 , 9 ( 1 ): 11497 .
NISHIDA-AOKI N , TOMINAGA N , KOSAKA N , et al . Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake [J ] . J Extracell Vesicles , 2020 , 9 ( 1 ): 1713527 .
DUSOSWA S A , HORREVORTS S K , AMBROSINI M , et al . Glycan modification of glioblastoma-derived extracellular vesicles enhances receptor-mediated targeting of dendritic cells [J ] . J Extracell Vesicles , 2019 , 8 ( 1 ): 1648995 .
SANTAVANOND J P , RUTTER S F , ATKIN-SMITH G K , et al . Apoptotic bodies: mechanism of formation, isolation and functional relevance [J ] . Subcell Biochem , 2021 , 97 : 61 - 88 .
MARTINS Á M , RAMOS C C , FREITAS D , et al . Glycosylation of cancer extracellular vesicles: capture strategies, functional roles and potential clinical applications [J ] . Cells , 2021 , 10 ( 1 ).
PINHO S S , REIS C A . Glycosylation in cancer: mechanisms and clinical implications [J ] . Nat Rev Cancer , 2015 , 15 ( 9 ): 540 - 555 .
KUNDU S , BENNETT Z , GUO J , et al . Investigation of intercellular trafficking of global glycosylphosphatidylinositol-anchored proteins using cell metabolic engineering and transwell coculture [J ] . Angew Chem Int Ed Engl , 2026 , 65 ( 5 ): e22420 .
BATISTA B S , ENG W S , PILOBELLO K T , et al . Identification of a conserved glycan signature for microvesicles [J ] . J Proteome Res , 2011 , 10 ( 10 ): 4624 - 4633 .
PRESCILLA-LEDEZMA A , LINARES F , ORTEGA-MUÑOZ M , et al . Molecular recognition of surface trans-sialidases in extracellular vesicles of the parasite Trypanosoma cruzi using atomic force microscopy (AFM) [J ] . Int J Mol Sci , 2022 , 23 ( 13 ).
SUN Z , LIH T M , WOO J , et al . Improving glycoproteomic analysis workflow by systematic evaluation of glycopeptide enrichment, quantification, mass spectrometry approach, and data analysis strategies [J ] . Anal Chem , 2024 , 96 ( 52 ): 20481 - 20490 .
LI M I , XU X , XI N , et al . Multiparametric atomic force microscopy imaging of single native exosomes [J ] . Acta Biochim Biophys Sin , 2021 , 53 ( 3 ): 385 - 388 .
KUNDU S , GUO J , ISLAM M S , et al . A new strategy to functionalize exosomes via enzymatic engineering of surface glycans and its application to profile exosomal glycans and endocytosis [J ] . Adv Sci , 2025 , 12 ( 18 ): e2415942 .
GURUNG S , PEROCHEAU D , TOURAMANIDOU L , et al . The exosome journey: from biogenesis to uptake and intracellular signalling [J ] . Cell Commun Signal , 2021 , 19 ( 1 ): 47 .
SMYTH T , PETROVA K , PAYTON N M , et al . Surface functionalization of exosomes using click chemistry [J ] . Bioconjug Chem , 2014 , 25 ( 10 ): 1777 - 1784 .
WU Y , WANG Y , LU Y , et al . Microfluidic technology for the isolation and analysis of exosomes [J ] . Micromachines (Basel) , 2022 , 13 ( 10 ).
MCDOWELL C T , LU X , MEHTA A S , et al . Applications and continued evolution of glycan imaging mass spectrometry [J ] . Mass Spectrom Rev , 2023 , 42 ( 2 ): 674 - 705 .
URBAN J , JIN C , THOMSSON K A , et al . Predicting glycan structure from tandem mass spectrometry via deep learning [J ] . Nat Methods , 2024 , 21 ( 7 ): 1206 - 1215 .
SCHAUER R . Sialic acids as regulators of molecular and cellular interactions [J ] . Curr Opin Struct Biol , 2009 , 19 ( 5 ): 507 - 514 .
YANG C , GUAN Z , PANG X , et al . Desialylated mesenchymal stem cells-derived extracellular vesicles loaded with doxorubicin for targeted inhibition of hepatocellular carcinoma [J ] . Cells , 2022 , 11 ( 17 ).
VAN HOUTUM E J H , BÜLL C , CORNELISSEN L A M , et al . Siglec signaling in the tumor microenvironment [J ] . Front Immunol , 2021 , 12 : 790317 .
GEURTSEN J , DRIESSEN N N , APPELMELK B J . Mannose-fucose recognition by DC-SIGN [M ] // Microbial Glycobiology . 2010 : 673 - 695 .
RUISS R , JOCHUM S , MOCIKAT R , et al . EBV-gp350 confers B-cell tropism to tailored exosomes and is a neo-antigen in normal and malignant B cells a new option for the treatment of B-CLL [J ] . PLoS One , 2011 , 6 ( 10 ): e25294 .
NIGAM S K , BUSH K T . Growth factor-heparan sulfate "switches" regulating stages of branching morphogenesis [J ] . Pediatr Nephrol , 2014 , 29 ( 4 ): 727 - 735 .
DANG S Y , LENG Y , WANG Z X , et al . Exosomal transfer of obesity adipose tissue for decreased miR-141-3p mediate insulin resistance of hepatocytes [J ] . Int J Biol Sci , 2019 , 15 ( 2 ): 351 - 368 .
ZHUANG W , LIU C , HONG Y , et al . Tumor-suppressive miR-4732-3p is sorted into fucosylated exosome by hnRNPK to avoid the inhibition of lung cancer progression [J ] . J Exp Clin Cancer Res , 2024 , 43 ( 1 ): 123 .
YU Y , DU H , WEI S , et al . Adipocyte-derived exosomal miR-27a induces insulin resistance in skeletal muscle through repression of PPARγ [J ] . Theranostics , 2018 , 8 ( 8 ): 2171 - 2188 .
ZHENG W , HE R , LIANG X , et al . Cell-specific targeting of extracellular vesicles through engineering the glycocalyx [J ] . J Extracell Vesicles , 2022 , 11 ( 12 ): e12290 .
XIANG Y , LIU J , LIU X , et al . Glycoengineered mesenchymal stem cell exosomes with dual-tissue targeting ameliorate glycolipid metabolism in type 2 diabetes mellitus [J ] . Chem Eng J , 2026 , 532 : 174202 .
TIAN W , ZAGAMI C , CHEN J , et al . Cell-based glycoengineering of extracellular vesicles through precise genome editing [J ] . N Biotechnol , 2024 , 83 : 101 - 109 .
LAUGHLIN S T , BERTOZZI C R . Metabolic labeling of glycans with azido sugars and subsequent glycan profiling and visualization via Staudinger ligation [J ] . Nat Protoc , 2007 , 2 ( 11 ): 2930 - 2944 .
JEWETT J C , BERTOZZI C R . Cu-free click cycloaddition reactions in chemical biology [J ] . Chem Soc Rev , 2010 , 39 ( 4 ): 1272 - 1279 .
LIM G T , YOU D G , HAN H S , et al . Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases [J ] . J Extracell Vesicles , 2021 , 10 ( 5 ): e12077 .
ZHANG W , YANG T , JIN T , et al . Enhancing chemotherapy-related immune responses via bioorthogonal metabolic engineering-driven tumor exosomes elimination [J ] . Adv Sci , 2025 , 12 ( 33 ): e06409 .
KOLB H C , FINN M G , SHARPLESS K B . Click chemistry: diverse chemical function from a few good reactions [J ] . Angew Chem Int Ed Engl , 2001 , 40 ( 11 ): 2004 - 2021 .
PALANIAPPAN K K , BERTOZZI C R . Chemical glycoproteomics [J ] . Chem Rev , 2016 , 116 ( 23 ): 14277 - 14306 .
ZHOU X , JAISWAL M , SHI J , et al . Efficient enzymatic glycan engineering of extracellular vesicles using nanomaterial-interfaced microfluidics [J ] . ACS Appl Mater Interfaces , 2025 , 17 ( 1 ): 2689 - 2700 .
ABREU C M , COSTA-SILVA B , REIS R L , et al . Microfluidic platforms for extracellular vesicle isolation, analysis and therapy in cancer [J ] . Lab Chip , 2022 , 22 ( 6 ): 1093 - 1125 .
HONG Y , ZHANG H , ZENG L , et al . Universal microfluidic platform for multifunctional surface modification of small extracellular vesicles [J ] . J Extracell Vesicles , 2025 , 14 ( 12 ): e70215 .
LENER T , GIMONA M , AIGNER L , et al . Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper [J ] . J Extracell Vesicles , 2015 , 4 : 30087 .
VOTTELER J , SUNDQUIST W I . Virus budding and the ESCRT pathway [J ] . Cell Host Microbe , 2013 , 14 ( 3 ): 232 - 241 .
LEVY D , WANG D , AFZALI H , et al . Hijacking exosome biogenesis: viral glycoproteins as modular scaffolds for engineering functionalized extracellular vesicles [J ] . Nanoscale , 2026 , 18 ( 4 ): 2252 - 2263 .
ELKHOURY K , KOCAK P , KANG A , et al . Engineering smart targeting nanovesicles and their combination with hydrogels for controlled drug delivery [J ] . Pharmaceutics , 2020 , 12 ( 9 ).
NI M , XING L , WANG Y , et al . Bioengineered milk-derived extracellular vesicles implementing high drug loading and membrane integrity for efficient oral drug delivery [J ] . Asian J Pharm Sci , 2025 , 20 ( 5 ): 101093 .
SATO Y , ZHANG W , BABA T , et al . Extracellular vesicle-liposome hybrids via membrane fusion using cell-penetrating peptide-conjugated lipids [J ] . Regen Ther , 2024 , 26 : 533 - 540 .
KELWICK R J R , WEBB A J , HELIOT A , et al . Opportunities to accelerate extracellular vesicle research with cell-free synthetic biology [J ] . J Extracell Biol , 2023 , 2 ( 5 ): e90 .
LI Y , MA X , ZHANG L , et al . Engineering yeast extracellular vesicle biogenesis through rewiring membrane trafficking pathways [J ] . Microb Biotechnol , 2026 , 19 ( 4 ): e70338 .
HENSON T , ARIZZI A , MEYER C , et al . Prototyping minimal extracellular vesicle mimetics using cell-free synthesis [J ] . ACS Nano , 2026 , 20 ( 9 ): 7385 - 7400 .
KELWICK R J R , WEBB A J , HELIOT A , et al . Hollow-fibre biomanufacturing and cell-free engineering of HEK293 extracellular vesicles [J/OL ] . bioRxiv , 2025 [ 2026-06-05 ] . https://doi.org/10.1101/2025.09.20.677537 https://doi.org/10.1101/2025.09.20.677537 .
DONDAPATI S K , STECH M , ZEMELLA A , et al . Cell-free protein synthesis: a promising option for future drug development [J ] . BioDrugs , 2020 , 34 ( 3 ): 327 - 348 .
LI M , SODER R , ABHYANKAR S , et al . Large-scale manufacturing of immunosuppressive extracellular vesicles for human clinical trials [J ] . Cytotherapy , 2025 , 27 ( 10 ): 1219 - 1228 .
MEGALAMANI P H , HARDUIN-LEPERS A , MANASA J , et al . Adhesion to aggression: unravelling sLe(a) and sLe(x) in cancer metastasis [J ] . Clin Exp Metastasis , 2025 , 42 ( 6 ): 58 .
CAI M , TIAN F , HAN J , et al . Genetically engineered extracellular vesicles expressing decoy protein TACI provide a therapeutic effect in systemic lupus erythematosus mouse model [J ] . J Control Release , 2025 , 384 : 113886 .
PI J , MA Y , WANG W , et al . Exosomal co-delivery of circRNA-TRAPPC6B and rifampicin for enhanced immunotherapy against tuberculosis [J ] . Int Immunopharmacol , 2025 , 167 : 115696 .
HUANG X , YANG J , HU Y , et al . Protective effects of GalNac-modified red blood cell-derived extracellular vesicles against liver diseases [J ] . Int J Nanomedicine , 2025 , 20 : 8993 - 9017 .
高天博 , 葛洋 , 安广宇 , 等 . 分子伴侣Cosmc或T-合酶缺失介导的异常O-糖基化调控结肠癌外泌体中微小RNA的表达 [J ] . 首都医科大学学报 , 2025 , 46 ( 03 ): 401 - 409 .
GAO T B , GE Y , AN G Y , et al . Abnormal O-glycosylation mediated by chaperone Cosmc or T-synthase deficiency regulates microRNA expression in colon cancer exosomes [J ] . J Cap Med Univ , 2025 , 46 ( 3 ): 401 - 409 .
LIU X M , MA L , SCHEKMAN R . Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates [J ] . Elife , 2021 , 10 .
SHARMA S , JIAO X , YANG J , et al . Extracellular exosomal RNAs are glyco-modified [J ] . Nat Cell Biol , 2025 , 27 ( 6 ): 983 - 991 .
ZHANG J , LI S , LI L , et al . Exosome and exosomal microRNA: trafficking, sorting, and function [J ] . Genomics Proteomics Bioinformatics , 2015 , 13 ( 1 ): 17 - 24 .
LIU F , XIA C , YU H , et al . Engineering exosomes for cancer therapy - modification technologies and subcellular targeting strategies: a review [J ] . Int J Pharm X , 2026 , 11 : 100473 .
王榕 , 高春芳 . 外泌体糖基化在肿瘤诊断和治疗中的应用进展 [J ] . 检验医学 , 2024 , 39 ( 04 ): 404 - 409 .
WANG R , GAO C F . Progress on the application of exosome glycosylation in tumor diagnosis and therapy [J ] . J Lab Med , 2024 , 39 ( 4 ): 404 - 409 .
PUAGSOPA J , TONGVISESKUL N , JAROENTOMEECHAI T , et al . Recent progress in developing extracellular vesicles as nanovehicles to deliver carbohydrate-based therapeutics and vaccines [J ] . Vaccines (Basel) , 2025 , 13 ( 3 ).
HAO Y , SU C , LIU X , et al . Bioengineered microglia-targeted exosomes facilitate Aβ clearance via enhancing activity of microglial lysosome for promoting cognitive recovery in Alzheimer's disease [J ] . Biomater Adv , 2022 , 136 : 212770 .
LIU X , HAO Y , HUANG Z , et al . Modulation of microglial polarization by sequential targeting surface-engineered exosomes improves therapy for ischemic stroke [J ] . Drug Deliv Transl Res , 2024 , 14 ( 2 ): 418 - 432 .
GU Z , YIN Z , SONG P , et al . Safety and biodistribution of exosomes derived from human induced pluripotent stem cells [J ] . Front Bioeng Biotechnol , 2022 , 10 : 949724 .
HU Y , YANG X , SHU F , et al . Smart exosomes: multimodal engineering strategies for logic-gated and stimuli-responsive precision theranostics [J ] . International Journal of Pharmaceutics , 2026 , 698 : 126846 .
THOMÈS L , JOERES R , AKDENIZ Z , et al . GlyContact analyzes glycan 3D structures at scale [J ] . Nat Commun , 2025 , 16 ( 1 ): 11136 .
ASFIYA R , XU L , PARAMANANTHAM A , et al . Physio-chemical modifications to re-engineer small extracellular vesicles for targeted anticancer therapeutics delivery and imaging [J ] . ACS Biomater Sci Eng , 2024 , 10 ( 2 ): 697 - 722 .
CAO J , LUO R , MIAO R , et al . Engineered exosome nanovesicles for delivery of antibodies to treat inflammatory bowel disease [J ] . Nat Commun , 2026 , 17 ( 1 ).
PFAFFL M W , KUBISTA M , VANDESOMPELE J , et al . MISEV and MIQE: integrating domain-specific and general standards to strengthen extracellular vesicle biomarker research [J ] . Extracell Vesicles Circ Nucl Acids , 2025 , 6 ( 4 ): 669 - 676 .
PR Newswire . Everglade助力Landmark Bio获得ARPA-H高达1830万美元资助 [EB/OL ] . [ 2026-06-04 ] . https://www.prnewswire.com/news-releases/everglade-helps-landmark-bio-secure-up-to-18-3-million-in-arpa-h-funding-302745022.html https://www.prnewswire.com/news-releases/everglade-helps-landmark-bio-secure-up-to-18-3-million-in-arpa-h-funding-302745022.html .
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