Chapter category: Antisense
Locked Nucleic Acids (LNA) and Medical Applications
Chapter authors:
Henrik Orum, Andreas Wolter and Lars Kongsbak
Much effort has been invested in altering the properties of synthetic oligonucleotides to make them more powerful tools in molecular biology, DNA based diagnostics and genomics, and as therapeutic agents. In particular, research has focused on providing DNA analogues which can enhance the affinity, selectivity, and nuclease resistance of oligonucleotides and improve their ability to cross biological membranes. As reviewed in earlier chapters, examples of promising analogues that provide at least some of these features include PNA, Morpholino, and 2'-MOE analogues. LNA is a novel class of bicyclic DNA analogues, which exhibit unprecedented affinity towards complementary DNA and RNA, as discussed in the previous chapter. Publications on LNA have mainly dealt with the synthesis of the various monomers (oxy-, thio-, amino- and ?-L-LNA) and the biophysical properties of oligonucleotides containing them. As LNA oligonucleotides have become commercially available, however, this picture is changing and several recent papers provide a glimpse of the promise that LNA holds as a research tool and as a diagnostic and therapeutic agent. This chapter reviews the present literature on LNA and provides data on LNA from the authors’ laboratories. Unless stated otherwise, all results relate to the Beta
