chapter  19
46 Pages

Locked Nucleic Acid

WithTroels Koch, Henrik Ørum

The concept of using single-stranded oligonucleotides to therapeutically inactivate RNA (antisense therapy) is enjoying a major renaissance. In part, interest is being driven by the prospect of effectively treating many diseases where the causative proteins have proven difficult or impossible to target by conventional drug approaches. Even greater impetus, however, comes from the explosive growth of information about the human genome and the genetic and molecular basis of disease, which has dramatically expanded the number of potential RNA targets for drug action over the past few years. In addition, enthusiasm is enhanced by the realization that antisense therapy may be the only realistic approach to target noncoding, regulatory RNAs, such as miRNAs, whose role in disease is being increasingly recognized. These regulatory microRNAs exert their function through Watson-Crick pairing to their target messenger RNAs providing strong evidence that effective antisense mechanisms are a natural biological feature of normal cell physiology.