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FRET imaging of glycoRNA on small extracellular vesicles enabling sensitive cancer diagnostics

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  • Tingju Ren

    (Northeastern University)

  • Yingzhi Zhang

    (The First Affiliated Hospital of China Medical University
    The First Affiliated Hospital of China Medical University)

  • Yuxiao Tong

    (Northeastern University)

  • Qi Zhang

    (Northeastern University)

  • Tianhao Wang

    (Northeastern University)

  • Yue Wang

    (Northeastern University)

  • Chunguang Yang

    (Northeastern University)

  • Zhangrun Xu

    (Northeastern University)

Abstract

Glycosylated RNAs (glycoRNAs), a recently discovered class of membrane-associated glyco-molecules, remain poorly understood in function and clinical value due to limited detection methods. Here, we show a dual recognition Förster resonance energy transfer (drFRET) strategy using nucleic acid probes to detect N-acetylneuraminic acid-modified RNAs, enabling sensitive, selective profiling of glycoRNAs on small extracellular vesicles (sEVs) from minimal biofluids (10 μl initial biofluid). Using drFRET, we identify 5 prevalent sEV glycoRNAs derived from 7 cancer cell lines. In a 100-patient cohort (6 cancer types and non-cancer controls), sEV glycoRNA profiles achieve 100% accuracy (95% confidence interval) in distinguishing cancers from non-cancer cases and 89% accuracy in classifying specific cancer types. Furthermore, drFRET reveal that sEV glycoRNAs specifically interact with Siglec proteins and P-selectin, which is critical for sEV cellular internalization. The drFRET strategy provides a versatile and sensitive platform for the imaging and functional analysis of sEV glycoRNAs, with promising implications for clinical applications.

Suggested Citation

  • Tingju Ren & Yingzhi Zhang & Yuxiao Tong & Qi Zhang & Tianhao Wang & Yue Wang & Chunguang Yang & Zhangrun Xu, 2025. "FRET imaging of glycoRNA on small extracellular vesicles enabling sensitive cancer diagnostics," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58490-2
    DOI: 10.1038/s41467-025-58490-2
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    References listed on IDEAS

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    1. Yusuke Yoshioka & Nobuyoshi Kosaka & Yuki Konishi & Hideki Ohta & Hiroyuki Okamoto & Hikaru Sonoda & Ryoji Nonaka & Hirofumi Yamamoto & Hideshi Ishii & Masaki Mori & Koh Furuta & Takeshi Nakajima & Hi, 2014. "Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen," Nature Communications, Nature, vol. 5(1), pages 1-8, May.
    2. Tingju Ren & Yingzhi Zhang & Yuxiao Tong & Qi Zhang & Tianhao Wang & Yue Wang & Chunguang Yang & Zhangrun Xu, 2025. "FRET imaging of glycoRNA on small extracellular vesicles enabling sensitive cancer diagnostics," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    3. Gang Wang & Jianlong Li & Linda Bojmar & Haiyan Chen & Zhong Li & Gabriel C. Tobias & Mengying Hu & Edwin A. Homan & Serena Lucotti & Fengbo Zhao & Valentina Posada & Peter R. Oxley & Michele Cioffi &, 2023. "Tumour extracellular vesicles and particles induce liver metabolic dysfunction," Nature, Nature, vol. 618(7964), pages 374-382, June.
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    1. Tingju Ren & Yingzhi Zhang & Yuxiao Tong & Qi Zhang & Tianhao Wang & Yue Wang & Chunguang Yang & Zhangrun Xu, 2025. "FRET imaging of glycoRNA on small extracellular vesicles enabling sensitive cancer diagnostics," Nature Communications, Nature, vol. 16(1), pages 1-19, December.

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