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

• Main Authors: Zhang, Yan, Wong, Chi Yan, Lim, Carine Z. J., Chen, Qingchang, Yu, Zhonglang, Natalia, Auginia, Wang, Zhigang, Pang, Qing You, Lim, See Wee, Loh, Tze Ping, Ang, Beng Ti, Tang, Carol, Shao, Huilin
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; Science::Medicine; Blood Sampling; Brain Tumor
• Online Access: https://hdl.handle.net/10356/171539
• Institution: Nanyang Technological University

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.