Locked nucleic acid (LNA) is a class of nucleic acid analogues possessing unprecedented binding affinity towards complementary RNA. LNA-type oligonucleotides are commercially available, are nontoxic, display increased RNA target accessibility, and can be designed to activate RNaseH or to function in steric block approaches. LNA-antisense, in particular, gapmer LNA, containing a central DNA or phosphorothioate-DNA segment flanked by LNA-gaps, rivals siRNA as the technology of choice for target validation and therapeutic applications.