Inhibition of miR-21 by 3′/5′-serinyl-capped 2′-O-methyl RNA interspersed with 2′-O-(2-amino-3-methoxypropyl) uridine units

Abstract

miRNAs are highly conserved class of small ncRNAs whose involvement in human pathophysiologies is extensively investigated. MiR-21 is a well established oncogenic miRNA whose deregulation plays a significant role in onset and progression of cancer. The need of novel approaches to downregulate miR-21 is rapidly expanding. Potent inhibition of miR-21 is achieved by chemically modified 2′-O-methyl RNA oligonucleotide. The serinol capping at 3′ and 5′ends and the interspersed 2′-O-(R-2-amino-3-methoxypropyl) uridine units enhance the nuclease resistance and efficacy of 2′-O-methyl RNA for the inhibition of miR-21. This represents a simple and novel modification for developing oligonucleotide-based therapeutics.