Sungkyunkwan University researchers led by Professor Jayeon Song, in collaboration with Massachusetts General Hospital(MGH), Harvard Medical School(HMS), and the Korea Research Institute of Bioscience and Biotechnology (KRIBB), have developed SCOPE (Self-amplified and CRISPR-aided Operation to Profile Extracellular Vesicles), an innovative diagnostic platform that dramatically improves the detection of extracellular vesicle (EV) mRNA. The study, titled “Amplifying mutational profiling of extracellular vesicle mRNA with SCOPE,” was published in the October 7, 2024 online edition of Nature Biotechnology (IF 33.1).

Extracellular vesicles (EVs) released into the bloodstream by tumor cells carry important molecular information, including mRNA. The low concentration of EV mRNA in blood samples makes it difficult to precisely detect using conventional diagnostic methods, and the lack of specificity in detecting mutant mRNA in EVs has limited cancer diagnosis. Therefore, the research team developed a genetic diagnostic platform that can accurately identify even low concentrations of cancer mutations by utilizing the CRISPR-Cas13a system to specifically detect EV mRNA and mutant mRNA.

The SCOPE (Self-amplified and CRISPR-aided Operation to Profile Extracellular Vesicles) diagnostic platform developed in this study uses CRISPR-Cas13a to distinguish specific cancer mutant sequences in extracellular vesicles down to a single nucleotide and trigger signal amplification, which can detect mutated genes (KRAS, BRAF, EGFR, and IDH1) with high sensitivity and specificity. It operates as a one-step isothermal reaction, providing rapid diagnostic results within 40 minutes with very low sample volumes. The developed diagnostic platform was applied to the early diagnosis of lung cancer in animal models, the diagnosis and recurrence monitoring of colorectal cancer patients, and the diagnosis of glioblastoma patients, confirming the clinical utility of liquid biopsy-based diagnostic systems.

The new CRISPR technology-based diagnostic platform is expected to revolutionize cancer diagnosis by providing a highly sensitive and specific diagnostic method for tracking tumor-derived cancer mutated genes.

*Paper: Amplifying mutational profiling of extracellular vesicle mRNA with SCOPE

Figure. Published online October 7 in Nature Biotechnology. CRISPR technology-based diagnostic technique for profiling mutant genes in the extracellular vesicle. Development of an integrated system that accurately recognizes mutant genes using CRISPR-Cas13a/crRNA and enables quick and convenient diagnosis through on-site diagnostic equipment.