Heteromultivalent scaffolds fabricated by biomimetic co-assembly of DNA-RNA building blocks for the multi-analysis of miRNAs

Heteromultivalent scaffolds with different repeated monomers have great potential in biomedicine, but convenient construction strategies for integrating various functional modules to achieve multiple biological functions are still lacking. Here, taking advantage of the heteromultivalent effect of dendritic nucleic acids and the specific biochemical properties of microRNAs (miRNAs), we assembled novel heteromultivalent nucleic acid scaffolds by biomimetic co-assembly of DNA-RNA building blocks. In our approach, two miRNAs were used to initiate and maintain dendritic structures in an interdependent manner; so, the heteromultivalent nanostructure can only form in the presence of both miRNAs. The proposed nanostructure can be used for one-step analysis of two miRNAs in an AND logic format. Taking miR-18b-5p and miR-342-3p which are associated with Alzheimer's disease as an example, a FRET sensing system was fabricated for the simultaneous analysis of two miRNAs within one hour at picomolar concentration. Further studies show that the designed device may have the potential to distinguish between AD patients and the healthy population by analysis of two miRNAs in CSF (cerebrospinal fluid) samples, suggesting its possible applicability in clinics.