LNA-i-miR-221

LNA-i-miR-221 is a 13-mer locked nucleic acid (LNA) inhibitor of microRNA-221 (miR-221) with a fully phosphorothioate (PS)-modified backbone. This first-in-class therapeutic agent works by specifically inhibiting miR-221, an oncogenic microRNA that is upregulated in various malignancies. The inhibition leads to downregulation of miR-221 expression, upregulation of canonical miR-221 targets (including CDKN1B/p27 and PTEN), restoration of drug sensitivity in resistant cancer cells, and induction of apoptosis. In multiple myeloma, LNA-i-miR-221 has been shown to reverse melphalan resistance in preclinical models. The agent has demonstrated anti-tumor activity against human xenografts in mice and favorable toxicokinetic profiles in rats and monkeys.