New trends in molecular pharmacology: artificial modulation of gene expression by transcription modifiers

Synthetic oligonucleotides have recently been the object of many investigations aimed to develop sequence-selective compounds able to modulate, either positively or negatively, transcription of eukaryotic and viral genes. This issue is of great interest in order to design anti-tumor compounds and anti-viral agents, as well as compounds able to induce cellular differentiation. Alteration of gene expression using transcription modifiers has been reported using DNA-binding drugs, such as distamycin, chromomycin, mithramycin, actinomycin D and CC-1065. In this review we describe recent reports on the use of (a) triple-helix forming oligonucleotides, (b) decoy molecules (either DNA or RNA) and (c) peptide nucleic acids for artificial modulation of gene expression. Triplex forming oligonucleotides recognizing promoter regions of eukaryotic and viral genes are able to inhibit the interaction between transcription factors and target DNA thereby altering transcription (anti-gene strategy). In a...