Oligonucleotides and their future potential as therapeutic agents

Abstract

This chapter describes the properties of triplex DNA and the rules governing its use in recognizing specific sequence in duplex DNA. Central to molecular biology is the well known paradigm that DNA makes RNA makes protein. However, despite the fact that this is an amplification system, with one copy of each gene generating many copies of RNA and protein, most therapeutic and pharmacological agents are targeted at proteins, which lie at the bottom of the pathway. The chapter focuses on attempts to overcome some of the current limitations in the use of triplex-forming oligonucleotides for recognition of mixed sequence DNAs under physiological conditions. Although DNA triple helix formation provides a means of achieving sequence-specific recognition of duplex DNA, and has been shown to be capable of controlling gene expression, the majority of in vitro studies to date have examined the formation of triplex structures on naked DNA.