Specific sequences of double-helical DNA can be recognized by oligonucleotides that form triple-helical complexes. A gene-specific pharmacological approach can be used whereby a synthetic oligonucleotide or an oligonucleotide analogue can be designed to selectively control the transcription of the targeted gene1. The oligonucleotide can be covalently attached to a molecule that can either induce an irreversible damage in the DNA (e.g., psoralen)2 or recruit a cellular enzyme to effect a site-specific modification of the target (e.g., cleavage by topoisomerase I)3. Alternatively, a gene therapy protocol can be developed whereby a DNA construct is used to generate a triplex-forming RNA within cells4,5. Another strategy based on clamp oligonucleotides6 allowed us to design oligonucleotide sequences that can bind to and form triple-helical complexes with specific targets on a single-stranded nucleic acid, (e.g., viral RNA) and inhibit nucleic acid-processing enzymes (e.g., reverse transcriptase).
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Helene, C. Sequence-Specific Gene Targeting Using Triplex Strategies. Nat Biotechnol 17 (Suppl 4), 28 (1999). https://doi.org/10.1038/70155
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DOI: https://doi.org/10.1038/70155
