LNA Antisense: A Review

Troels      Koch

Abstract

Over the past 10-15 years LNA (Locked Nucleic Acid) has taken a central position in nucleic acid chemistry and biology. The enhanced hybridization properties against both DNA and RNA have become a new reference in the field and proven to be enabling for many application in life sciences. For therapeutic use as RNA targeting drugs LNA enable the design of potent antisense oligonucleotides. Much effort has been dedicated to get efficient delivery of RNA targeting drugs, but in contrast to e.g. siRNA duplexes it has been demonstrated that LNA oligonucleotides are taken up by cells without added deliver vehicles in an active state (gymnotic delivery). Here, the fundamental properties of LNA are reviewed together with the recent and most advanced pre-clinical/clinical LNA data.

Keywords: LNA (Locked Nucleic Acid), Antisense, hybridization, Bicyclic, Nucleoside structure, Property space, Gymnosis, Drug discovery, Pharmacokinetics, Pharmacodynamics, Non-human primate, Pre-clinical, ApoB, PCSK9, HCV, Clinical