Multiplexed RNA profiling by regenerative catalysis enables blood-based subtyping of brain tumors

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Abstract

Current technologies to subtype glioblastoma (GBM), the most lethal brain tumor, require highly invasive brain biopsies. Here, we develop a dedicated analytical platform to achieve direct and multiplexed profiling of circulating RNAs in extracellular vesicles for blood-based GBM characterization. The technology, termed ‘enzyme ZIF-8 complexes for regenerative and catalytic digital detection of RNA’ (EZ-READ), leverages an RNA-responsive transducer to regeneratively convert and catalytically enhance signals from rare RNA targets. Each transducer comprises hybrid complexes – protein enzymes encapsulated within metal organic frameworks – to configure strong catalytic activity and robust protection. Upon target RNA hybridization, the transducer activates directly to liberate catalytic complexes, in a target-recyclable manner; when partitioned within a microfluidic device, these complexes can individually catalyze strong chemifluorescence reactions for digital RNA quantification. The EZ-READ platform thus enables programmable and reliable RNA detection, across different-sized RNA subtypes (miRNA and mRNA), directly in sample lysates. When clinically evaluated, the EZ-READ platform established composite signatures for accurate blood-based GBM diagnosis and subtyping.

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Zhang, Y., Wong, C. Y., Lim, C. Z. J., Chen, Q., Yu, Z., Natalia, A., … Shao, H. (2023). Multiplexed RNA profiling by regenerative catalysis enables blood-based subtyping of brain tumors. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-39844-0

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