Silencing of microRNAs in vivo with ‘antagomirs’

To develop a pharmacological approach for silencing miRNAs in vivo, a small interfering double-stranded RNAs (siRNAs) engineerred with certain "drug-like" properties such as chemical modifications for stability and cholesterol conjugation for delivery have been shown to achieve therapeutic silencing fo an endogeous gene in vivo. To explore the potential of these synthetic RNA analogues to silence endogenous miRNAs, chemical modified, cholesterol-conjugated antagomir, antagomir-122 which sequence designed for miR-122, an abundant, liver-specific miRNA. Antagomir-122 was synthesized starting from a hydroxyprolinol-linked cholesterol solid support14 and 2''-OMe phosphoramidites. This compound was administered to mice by intravenous injection at normal pressure. Administration of antagomir-122 resulted in a marked decrease in endogenous miR-122 levels as detected by northern blots while unmodified single-stranded RNA (anti-122) had no effect on levels of hepatic miRNA-122. Click on PDF link below for this article!