Specific Inhibition of MicroRNA Processing Using l‑RNA Aptamers

<i>In vitro</i> selection was used to obtain l-RNA aptamers that bind the distal stem-loop of various precursor microRNAs (pre-miRs). These l-aptamers, termed “aptamiRs”, bind their corresponding pre-miR target through highly specific tertiary interactions rather than Watson–Crick pairing. Formation of a pre-miR–aptamiR complex inhibits Dicer-mediated processing of the pre-miR, which is required to form the mature functional microRNA. One of the aptamiRs, which was selected to bind oncogenic pre-miR-155, inhibits Dicer processing under simulated physiological conditions, with an IC₅₀ of 87 nM. Given that l-RNAs are intrinsically resistant to nuclease degradation, these results suggest that aptamiRs might be pursued as a new class of miR inhibitors