MiRNA-masking antisense oligonucleotides technology (miR-mask) is an anti-microRNA antisense oligodeoxyribonucleotide (AMO) approach of a different sort. A standard miR-mask is single-stranded 2′-O-methyl-modified oligoribonucleotide (or other chemically modified) that is a 22-nt antisense to a protein-coding mRNA as a target for an endogenous miRNA of interest. Instead of binding to the target miRNA like an AMO, an miR-mask does not directly interact with its target miRNA but binds to the binding site of that miRNA in the 3′ UTR of the target mRNA by fully complementary mechanism. In this way, the miR-mask covers up the access of its target miRNA to the binding site so as to derepress its target gene (mRNA) via blocking the action of its target miRNA. The anti-miRNA action of an miR-mask is gene-specific because it is designed to be fully complementary to the target mRNA sequence of an miRNA. The anti-miRNA action of an miR-mask is miRNA-specific as well because it is designed to target the binding site of that particular miRNA. The miR-mask approach is a valuable supplement to the AMO technique; while AMO is indispensable for studying the overall function of an miRNA, the miR-mask might be more appropriate for studying the specific outcome of regulation of the target gene by the miRNA. This technology was first established by my research group in 2007 (Xiao et al., J Cell Physiol 212:285–292; Wang et al., J Mol Med 86:772–783, 2008) and a similar approach with the same concept was subsequently reported by Schier’s laboratory (Choi et al., Science 318:271–274, 2007).