Fret Imaging Of Glycorna On Small Extracellular Vesicles Enabling Sensitive Cancer Diagnostics Tingju Ren Yingzhi Zhang Yuxiao Tong Qi Zhang Tianhao Wang Yue Wang Chunguang Yang Zhangrun Xu by Tingju Ren & Yingzhi Zhang & Yuxiao Tong & Qi Zhang & Tianhao Wang & Yue Wang & Chunguang Yang & Zhangrun Xu 101038/S41467025584902 instant download after payment.

Glycosylated RNAs (glycoRNAs), a recently discovered class of membraneassociated glyco-molecules, remain poorly understood in function and clinicalvalue due to limited detection methods. Here, we show a dual recognitionFörster resonance energy transfer (drFRET) strategy using nucleic acid probesto detect N-acetylneuraminic acid-modified RNAs, enabling sensitive, selectiveprofiling of glycoRNAs on small extracellular vesicles (sEVs) from minimalbiofluids (10 μl initial biofluid). Using drFRET, we identify 5 prevalent sEVglycoRNAs derived from 7 cancer cell lines. In a 100-patient cohort (6 cancertypes and non-cancer controls), sEV glycoRNA profiles achieve 100% accuracy(95% confidence interval) in distinguishing cancers from non-cancer cases and89% accuracy in classifying specific cancer types. Furthermore, drFRET revealthat sEV glycoRNAs specifically interact with Siglec proteins and P-selectin,which is critical for sEV cellular internalization. The drFRET strategy provides aversatile and sensitive platform for the imaging and functional analysis of sEVglycoRNAs, with promising implications for clinical applications.