LidNA, a novel miRNA inhibitor constructed with unmodified DNA

Many miRNA inhibitors have been developed and they are chemically modified oligonucleotides such as 2′-O-methylated RNA and locked nucleic acid (LNA). Unmodified DNA was not yet reported as a miRNA inhibitor because of the low affinity of DNA/miRNA compared to mRNA/miRNA. We designed a structured unmodified DNA that significantly inhibits miRNA function. The clue structure for activity is the miRNA binding site between double stranded regions which is responsible for the miRNA inhibitory activity and tight binding to miRNA. We developed the miRNA inhibitor constructed with unmodified DNA, and named it LidNA, DNA that puts a lid on miRNA function.

► We designed a structured DNA, LidNA, that significantly inhibits miRNA.
► The inhibitory effects of LidNA are superior to LNA and 2′-O-Me-RNA inhibitors.
► The miRNA binding site between double stranded regions is required for miRNA inhibition.
► The affinity of LidNA-type DNA to miRNA is over 1000 times higher than that of ssDNA.
► LidNA has higher ka and kd values than LNA and 2′-O-Me-RNA.