Dual-microRNA-controlled double-amplified cascaded logic DNA circuits for accurate discrimination of cell subtypes

Accurate discrimination between different cells at the molecular level is particularly important for disease diagnosis. Endogenous RNAs are such molecular candidates for cancer cell subtype identification. But the key is that there is often low abundance of RNAs in live cells, or some RNAs are often shared by multiple types of cells. Thus, we have designed dual-microRNA-controlled double-amplified cascaded logic DNA circuits for cancer cell subtype identification. The basic idea is to improve sensitivity by cascading DNAzyme and hybridization chain reaction (HCR), and improve accuracy by simultaneous detection of miR-122 and miR-21. The in-tube and in-cell experimental results show that the cascaded logic DNA circuits can work and serve to differentiate the liver cancer cells Huh7 from other normal cells and cancer cells. We anticipate that this design can be widely applied in facilitating basic biomedical research and accurate disease diagnosis.