Table 1.

miRNA-based therapeutic approaches

Method	Definition	Mechanism of action	Clinical trial stage
AMOs73	A single-stranded, RNA molecule designed to be complementary to a selected miRNA	Competitive inhibition of mature miRNA by Watson-Crick binding	Preclinical studies
2’-O- modified AMOs	Modification of 2’-OH to 2’-O’methyl- and 2’-O’methoxyethyl- groups	Competitive inhibition of mature miRNA by Watson-Crick binding	Phase I clinical trial
Antagomirs43	AMOs modified to have a phosphorothiolate backbone and conjugated with cholesterol	Competitive inhibition of mature miRNA; detailed mechanism still unclear	Preclinical studies
LNA anti-miRNAs45. 46	Addition of an extra methylene bridge connecting the 2′-O atom and the 4′-C atom and ‘locks’ the ribose ring in a C3’-endo or C2’-endo conformation	High-affinity Watson-Crick hybridization with their RNA target molecules - Inhibition	Phase I and II clinical trials
miRNA sponges51	RNA transcripts with multiple tandom repeats of miRNA binding sites for an endogenous miRNA	Stably interact with corresponding miRNA and prevent its interaction with its target mRNAs	Preclinical studies
miRNA masks53	Single-stranded 2’-O’methyl-modified antisense oligonucleotides with entire complementary to the miRNA binding sites in the 3’-UTR of the target mRNA	‘Mask’ the target mRNA from the endogenous miRNA and thus prevent its suppression	Preclinical studies
Small molecule inhibitors of miRNAs (SMIRs)39, 40, 54	Small-molecule chemical compounds that interfere with miRNA biogenesis or matuation	Block specific miRNAs by structure-based docking onto the precursor or mature form of the miRNAs	Preclinical studies
miRNA expression vectors74	Expression vectors that express a specific type of miRNA	Restoration of the expression and function of a specific miRNA	Preclinical studies
miRNA mimics74	Small, chemically modified (2’-O’methoxy) RNA duplexes that can be loaded into RISC and achieve the downstream inhibition of the target mRNAs	Assist the miRNA function	Phase I clinical trials