Fig. 6.
Pharmacologic approaches to target microRNAs (miRNAs). miRNAs can be targeted for treatment. (A) Chemically modified RNA molecules can function as miRNA inhibitors (anti-miRs). They bind to specific endogenous miRNAs and inhibit their function. This will rescue a specific miRNA from miRNA-mediated regulation. The most successful chemical modification increasing the hybridization properties of the RNA molecule are locked nucleic acids (LNAs). An anti-miR that recently successfully entered a clinical phase II study is SPC 3649 that binds to and blocks the function of miR-122, an miRNA that is required for the hepatitis C virus replication.103 (B) miRNA mimics are double-stranded miRNAs that intend to mimic the endogenous miRNA. They comprise the same nucleotide sequence as the desired endogenous miRNA and are designed to target the same mRNAs by binding in the 3 prime untranslated region (3′UTR) and recruiting RNA-induced silencing complex (RISC). A miR-34 mimic, MRX34, currently entered a phase I clinical trial (ClinicalTrials.gov identifier: NCT01829971) to be tested in patients with primary liver cancer or patients with liver metastasis from other cancers. In this study intended to investigate safety, pharmacokinetics, and pharmacodynamics of MRX34, the drug will be administered intravenously (IV). 2′-OMe = 2′-O-methyl; 2′-OME = 2′-O-methyoxyethyl; s.c. = subcutaneously.