Abstract
Publisher Summary Many excellent reviews and monographs have been written describing the chemistry and biological activity of various antisense and antigene oligonucleotides. This chapter focuses on two lines of research that are aimed at the development of antisense and antigene oligonucleotide analogs. The first line of research involves the development of nuclease-resistant antisense oligonucleotide analogs, the oligonucleoside methylphosphonates. The second line of research involves the development of nucleoside and oligonucleotide analogs that can be used to recognize sequences in double-stranded DNA. Antisense oligonucleotides are designed to interact with cytoplasmic messenger RNA (mRNA) or with precursor mRNA in the nucleus. Antigene oligonucleotides are designed to bind to double-stranded DNA via the formation of triple-stranded complexes (triplexes). Antisense oligonucleotides depend on Watson–Crick hydrogen-bonding interactions between an oligomer and its target, whereas antigene oligonucleotides make use of Hoogsteen or reversed-Hoogsteen hydrogen-bonding schemes. Antisense and antigene oligonucleotide analogs hold great promise for the design of reagents that can be used to inhibit gene expression selectively at either the mRNA or DNA level.
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