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CHAPTER 8. Research and Development of Oligonucleotides Targeting MicroRNAs (miRNAs)

MicroRNAs (miRNAs) are small, highly conserved, endogenous RNAs that regulate large parts of the gene expression in cells. Dysregulation of a miRNA's function, caused, for example, by mutations, loss of expression, disrupted maturation, or reduced stability etc., may cause or contribute to the progression of disease states. Oligonucleotides complementary to a miRNA (antimiRs) have been developed to bind and inhibit their function, both as tools and as potential therapeutics. Medicinal chemistry efforts designed to modify antimiRs so that they may be used in vivo have followed a similar path to those for antisense, splice-modulating and small interfering RNAs. Here we review some of the chemical modifications that have been employed in antimiRs and how some of these have advanced to clinical testing. We also describe how knowledge of the mechanisms of miRNA biogenesis and mRNA targeting is influencing the next generation of antimiR reagents.