Liquid biopsy research is advancing quickly, yet common approaches such as circulating DNA, exosomal proteins, and standard RNA profiling still face limits in sensitivity, specificity, and biological resolution. The discovery of glyco-RNA—RNAs modified with glycan structures and displayed on membrane surfaces—offers a new direction by combining the coding features of nucleic acids with the spatial recognition properties of glycans. A recent Nature Communications study introduced a dual-recognition FRET imaging strategy that enables sensitive in situ detection of glyco-RNA on extracellular vesicles, revealing its potential to support earlier and more precise biomarker exploration. As this field expands, glyco-RNA is expected to drive new opportunities in liquid biopsy development and reshape how molecular signals are captured and interpreted.
Glyco-RNAs offer unprecedented opportunities for early disease detection and functional studies due to their dual RNA–glycan properties. Overcoming current technical barriers is crucial to fully realize their diagnostic and translational potential.
The discovery of glyco-RNA represents a paradigm shift in the field of epitranscriptomics. These hybrid molecules exhibit remarkable potential because of their unusual chemical features: they combine the sequence specificity of RNA with the structural diversity of glycans, offering a much higher information capacity than single-component biomolecules. As membrane-anchored entities, glyco-RNAs also demonstrate increased stability in circulation, making them easier to capture through analytical systems. In addition, their ability to directly engage immune receptors such as Siglecs suggests active roles in intercellular communication and immune modulation.
Despite this promise, glyco-RNA research faces several substantial technical barriers. Current analytical tools cannot provide in situ visualization or quantitative assessment without extensive preprocessing. Expression patterns and potential diagnostic relevance remain largely unexplored. Studying their dynamic functions and interactions in their native state is still extremely challenging. At the same time, traditional methods are low-throughput and operationally complex, far from meeting the practical requirements of large-scale screening.
Fig. 1: Presence of glycoRNAs on sEVs1,4.
The Nature Communications study outlines a clear roadmap for overcoming the current barriers in glyco-RNA research. One major focus is the development of in situ imaging technologies that require no metabolic labeling and enable multiplexed quantitative analysis—an essential step for advancing from qualitative observations to precise molecular measurement. The work also highlights the importance of expanding the analytical scope from the cell surface to small extracellular vesicles, as establishing detection strategies based on biofluids is a necessary pathway toward future liquid biopsy applications.
The proposed technological evolution can be summarized in three stages:
Fig. 2: Development of drFRET for in situ imaging of sEV glyco-RNAs2,4.
The study also emphasizes the importance of creating a tightly integrated research loop in which technological innovation and biological discovery reinforce each other. Only by advancing detection methods while simultaneously investigating glyco-RNA function can the field build a productive ecosystem and accelerate progress toward clinical translation.
The drFRET technique represents a major leap forward in detecting glyco-RNAs with unprecedented specificity and sensitivity. By combining dual-recognition probes, it enables direct visualization and quantitative analysis of sEV-associated glyco-RNAs under near-physiological conditions.
The core innovation of the drFRET technique lies in its dual-recognition design, which fundamentally addresses the challenge of achieving specificity within complex biological environments. The method simultaneously employs a glycan-recognition probe and an RNA-sequence probe: the glycan probe selectively targets N-acetylneuraminic acid, while the RNA probe hybridizes with high precision to the intended RNA sequence. A FRET signal is generated only when both probes bind to the same molecule within approximately 10 nanometers, and this nanoscale spatial requirement ensures exceptional specificity.
This physics-based specificity—driven by energy transfer principles—eliminates false-positive signals at the source and enhances detection accuracy by an order of magnitude compared with traditional approaches. The design provides a solid foundation for quantitative glyco-RNA measurement and marks a major technological advancement, opening new opportunities for functional studies and future diagnostic applications.
The research team established a fully integrated development pipeline that spans basic investigation to clinical validation. In the early phase, metabolic labeling combined with click chemistry enabled the first confirmation of glyco-RNAs on the surface of sEVs, establishing a strong biological basis for subsequent optimization. A series of rigorous control experiments—including enzyme digestion and inhibitor treatments—were then carried out to confirm the specificity and robustness of the method.
Fig. 3: In situ FRET imaging of glyco-RNAs on cancer-derived sEVs3,4.
The clinical validation phase delivered striking outcomes:
Across 88 cancer samples and 12 healthy controls—including breast, pancreatic, liver, and other cancers—the combined signature of five glyco-RNAs demonstrated exceptionally strong diagnostic performance. This level of accuracy represents a significant milestone for liquid biopsy research and provides compelling evidence supporting glyco-RNA as a promising new diagnostic marker.
Beyond diagnostics, drFRET serves as a powerful functional research tool, offering direct insights into the biological roles of glyco-RNAs. By replacing the glycan probe with Cy3-labeled Siglec-10, researchers achieved the first in situ visualization of direct interactions between glyco-RNAs and immune receptors. This approach overcomes the constraints of traditional biochemical assays and enables molecular interaction studies under near-physiological conditions.
Complementary validation experiments showed that RNase A treatment reduced the binding signal by ~80%, confirming that glyco-RNAs—not other glycan-containing structures—were responsible for the observed interactions. Functionally, the removal of glyco-RNAs or glycans from sEV surfaces significantly reduced their uptake by endothelial cells, with a decrease exceeding 70%.
These findings carry important implications on three levels:
Despite recent breakthroughs at the laboratory level, translating the drFRET technology into a broadly deployable clinical tool continues to face significant hurdles. The complexity of probe design remains one of the primary barriers. Each new target requires customized, sequence-specific probe development, resulting in lengthy optimization cycles and high costs—factors that restrict the scalability and wider adoption of the technology. The lack of standardized workflows further complicates translation, as current manual procedures fall short of clinical requirements for throughput, reproducibility, and operational simplicity.
Another major constraint is the limitation of ensemble measurements. Population-averaged signals cannot capture the underlying heterogeneity of sEVs, whereas precision diagnostics ultimately require single-vesicle resolution to enable truly individualized analysis. Additionally, the field still lacks a closed-loop system that connects omics-based biomarker discovery with imaging-based validation. This disconnect slows the development pipeline for novel biomarkers and adds significant uncertainty to the translational pathway.
A notable challenge is that current detection strategies primarily target known glyco-RNA sequences. Discovering entirely new biomarkers requires integration with other omics platforms, increasing both workflow complexity and R&D costs. Building a complete industrial pipeline—from biomarker discovery to validation and eventually clinical deployment—remains the central challenge for commercializing glyco-RNA–based diagnostics.
In advancing the industrialization of glyco-RNA technologies, BOC Sciences leverages its extensive expertise in glycoscience to provide comprehensive technical support for researchers. Through advanced glycan profiling platforms, we help decode complex glycan structures in biological samples, offering essential insights into glyco-RNA glycosylation patterns. Our customized glycan modification and functionalization services further enable investigations into how glycan structures influence RNA stability and function, supporting deeper biological exploration.
With dual expertise in nucleic acid chemistry and glycochemistry, BOC Sciences offers specialized support for glyco-RNA probe design and optimization. We place particular emphasis on bridging fundamental research with practical application needs, providing integrated solutions that span glycan structure analysis to functional modification—helping researchers overcome critical translational barriers.
Future collaboration directions include:
Through continued technological innovation and industry partnerships, we aim to accelerate the transition of glyco-RNA research from laboratory discovery to clinical implementation. Together with researchers worldwide, we strive to unlock the full diagnostic potential of glyco-RNA in early cancer detection and personalized healthcare, contributing meaningful advancements to precision medicine.
In the cutting-edge, interdisciplinary field of glyco-RNA research, scientists face numerous challenges spanning biomarker discovery to functional validation. Leveraging over 20 years of expertise in glycoscience and nucleic acid chemistry, BOC Sciences provides comprehensive solutions from basic research to translational applications, positioning itself as a trusted partner in advancing glyco-RNA innovation.
One of the central challenges in glyco-RNA research is obtaining functionalized glycans with specific structures. BOC Sciences offers comprehensive custom glycan modification and functionalization services, tailored to support the development of tools necessary for glyco-RNA studies.
Our technical team brings extensive experience in glycan synthesis, capable of designing and producing diverse glycan structures according to research needs—from simple monosaccharide modifications to complex branched oligosaccharides. We provide selective glycosylation, optimized protecting group strategies, and functional group incorporation, creating specialized glycans for probe development, receptor binding studies, or cellular functional assays.
For functionalization, we offer a range of bioconjugation techniques, enabling the targeted attachment of glycans to fluorophores, biotin, proteins, or other biomolecules. These functionalized glycans can be directly applied in receptor interaction assays, or other biochemical investigations, providing essential reagents for exploring glyco-RNA biological functions.
To address the need for detailed analysis of complex glycan compositions in glyco-RNA research, we offer professional glycan profiling services. Our platform integrates advanced enzymatic digestion, glycan labeling, and cutting-edge LC-MS, UPLC, and capillary electrophoresis technologies, delivering accurate and reproducible glycan data to elucidate glyco-RNA glycosylation patterns.
Our services cover the complete glycan analysis workflow, including sample preparation, glycan release, labeling, purification, instrumental analysis, and data interpretation. Using HILIC-UPLC, capillary electrophoresis, and mass spectrometry, we precisely characterize glycan structures, modification patterns, and relative abundances, providing reliable structural insights for glyco-RNA research.
We have optimized protocols for low-volume samples, ensuring high-quality glycan profiling even under limited sample conditions. The resulting data can directly support biomarker discovery, glycan structure–function studies, and the development of glyco-RNA diagnostic models.
BOC Sciences adheres to the highest quality standards, with all services rigorously validated to ensure data reliability and reproducibility. Our scalable production capabilities support all stages from early research to clinical applications, whether for milligram-level exploratory studies or kilogram-scale production.
Our expert team, with extensive experience in glycobiology, provides 24/7 technical consultation and project support. Whether your focus is glyco-RNA biomarker discovery, probe development, or functional mechanism research, we deliver customized solutions to accelerate your scientific progress.
Glyco-RNA, as a novel biomolecule bridging nucleic acid coding information with glycan recognition functions, is reshaping research paradigms in liquid biopsy and intercellular communication. From fundamental research to clinical application, the field demonstrates tremendous translational potential and growth opportunities.
We invite you to explore BOC Sciences’ glycobiology solutions today. Visit our website to learn more about our glycan modification, functionalization, and glycan profiling services. Our expert team is ready to provide personalized technical consultation and project support, helping advance glyco-RNA research from the lab to clinical translation.
Contact Us: Submit your project requirements, and our technical specialists will respond to tailor the most suitable research solution for your needs. Let’s collaborate to achieve new breakthroughs in this emerging field.
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