Targeting non-coding RNA family members with artificial endonuclease XNAzymes.

Non-coding RNAs (ncRNAs) offer a wealth of therapeutic targets for a range of diseases. However, secondary structures and high similarity within sequence families make specific knockdown challenging. Here, we engineer a series of artificial oligonucleotide enzymes (XNAzymes) composed of 2'-deoxy-2'-fluoro-β-D-arabino nucleic acid (FANA) that specifically or preferentially cleave individual ncRNA family members under quasi-physiological conditions, including members of the classic microRNA cluster miR-17~92 (oncomiR-1) and the Y RNA hY5.