Towards the Targeted Modulation of Gene Expression by Modified Triplex-Forming Oligonucleotides

Keith   R.   Fox; David   A.   Rusling; Victoria   J.   Broughton-Head; Tom      Brown

Abstract

DNA triple helices are formed when a third nucleic acid strand binds within the major groove of a DNA duplex. The formation of these structures can be used to achieve selective recognition of extended DNA sequences, which may be useful in several medical and biotechnological applications. Although triplex formation is relatively straightforward in vitro, there are several problems that limit its use in cellular contexts, including a low stability at physiological pH and a requirement for oligopurine.oligopyrimidine target sites. There are also concerns about the uptake, localisation and degradation of triplex-forming oligonucleotides (TFOs) in cells, as well as the accessibility of chromosomal DNA. Major advances in the chemistry of DNA triplex formation have been made in the last few years and this review highlights the current status of this approach, with an emphasis on the use of chemically modified TFOs for gene targeting.

Keywords: DNA sequences, Transcription Initiation, Gene Expression, yeast systems, Parallel triplexes