Enhancing the stability of small oligonucleotides to prolong circulation and meanwhile increasing target specificity are major concerns for therapeutic applications. Various kinds of modifications in backbones, sugars or even analogs have already been studied extensively [for reviews, see (22, 23) ] to meet these requirements. Locked nucleic acid (LNA) is a rather novel nucleic acid analog comprising a class of bicyclic high-affinity RNA analogs in which the furanose ring of LNA monomers is conformationally locked in an RNA-mimicking C3 0 -endo/ N-type conformation (24) . The LNA modification also resists degradation by cellular nucleases. Furthermore, introducing LNA into DNA or RNA oligonucleotides improves the affinity for complementary sequences and increases the melting temperature by several degrees (25) . A recent study showed that LNA/DNA mix-mers against miRNA-122 can be acutely administered at high dosage with long lasting effects without any evidence of LNA-associated toxicities or histopathological changes in the studied animals (26) . These data suggests that LNA is a promising candidate for small oligonucleotide applications.