Researchers at Mass General Work on Blood Test for Early Cancer Detection

A team at Mass General Hospital is “working to develop a blood test for detecting cancers earlier, whether new diagnoses or recurrence” involving a new approach called SCOPE.

SCOPE, which stands for “self-amplified and CRISPR-aided operation to profile EVs,” is an approach that uses “extracellular vesicles (EVs)” to detect cancer’s signatures by encapsulating and protecting mRNA.

EV mRNA “provides a richer molecular snapshot of actionable and relevant tumor mutations and information on how tumors may resist treatment.” Analyzing mRNA offers advantages over traditional analysis of ctDNA, as the former is “more abundant” than the latter and “can provide deeper insights into the functional state of tumors.”

The research team took inspiration from CRISPR technology, which is a “powerful tool in molecular diagnostics because it can target and cut DNA or RNA at precise locations.” Cas proteins, which are used with CRISPR, can “recognize and target specific nucleic acids.” Using these methods, the team amplified “both the target mRNA and the detection signal simultaneously” to “precisely identify single-nucleotide polymorphisms in EVs.”

SCOPE “successfully distinguished KRAS wild-type mRNA in EVs from key mutations such as G12C, G12D, G12S, and G12V, even outperforming a powerful commercial assay designed for these variants.” This shows that SCOPE “identifies circulating EVs carrying genetic mutations that match those detected in corresponding tumor tissues, confirming that EVs are reliable biomarkers for liquid biopsy. This platform holds great potential for cancer research and could help us unravel the mechanisms behind cancer progression and resistance, assess treatment responses, and identify cancer cells that remain after treatment (a concept known as minimal residual disease).” The technology could also potentially be fitted for use in fields like infectious diseases.