Triplex-forming oligonucleotides as modulators of gene expression.
Triplex-forming oligonucleotides (TFOs) have gained prominence in the recent years because of their potential applications in antigene therapy. In particular they have been used as (i) inducers of site-specific mutations, (ii) reagents that selectively and specifically cleave target DNA, and (iii) as modulators of gene expression. In this mini-review, we have made an attempt to highlight the characteristics of these TFOs and the effects of various modifications in the phosphate backbone as well as in the purine and pyrimidine moieties, which contribute to the stability and efficiency of triplex formation. Studies to explore the mechanism of down-regulation of transcription of various genes suggest that at least some TFOs exert their effect by inhibiting binding of specific transcription factors to their cognate cis-acting elements. Recent reports indicate the presence of these potential triplex-forming DNA structures in the genomes of prokaryotes and eukaryotes that may play a major role in target site selection and chromosome segregation as well as in the cause of heritable diseases. Finally, some potential problems in the development of these TFOs as antigene therapeutic agents have also been discussed.
Guntaka
Ramareddy V
RV
Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Ave., Memphis, TN 38163, USA. rguntaka@utmem.edu
Varma
Balwantkumar R
BR
Weber
Karl T
KT
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D005057:Eukaryotic Cells / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016678:Genome; D006801:Humans; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology / Q000633:toxicity; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009841:Oligonucleotides / Q000737:chemistry* / Q000494:pharmacology*; D011387:Prokaryotic Cells / Q000502:physiology
D009153:Mutagens; D009841:Oligonucleotides; D004247:DNA