History and Development of Nucleotide Analogues in Nucleic Acids Drugs

Abstract

The nucleic acid-based drug discovery approach is now being recognized as a major platform in addition to small molecules and peptide- or protein-based platforms. Advancement in nucleic acid based drugs has been aided by the chemistry of oligonucleotides and nucleic acids in providing drug-like properties. Early experience was gained with respect to the use of the chemistry of oligonucleotides for use as antisense agents. These chemical structure–activity relationship studies included modification of the backbone, heterocyclic bases and sugars, or combinations thereof. In this chapter we discuss early developments in the chemistry of nucleic acids that have guided the design and successful development of antisense drugs as well as nucleic acid-based platforms employing many other mechanisms, including aptamers, siRNA, exon skipping, ribozyme, microRNA and non-coding RNA and immune modulation.