The growing interest raised in olignucleotide-directed triple helix formations ('anti-gene strategy!) is due to their potential biological and therapeutical applications for controling gene expression at both transcriptional and replicational levels. The present project is aimed at developing new approaches to extend the range of double-stranded DNA recognition via oligonucleotide-directed triple helix formation. The ultimate goal is to apply 'antigene strategy' to any DNA target sequence with biological interest without sequence limitation as it is currently restricted to polypurine-polypyrimidine tracts. Syntheses of modified oligonucleotides containing triple helix-specific stabilizers are envisioned. Their abilities to form stable extended triple helices under physiological conditions will be evaluated. Results are expected in inhibition of gene expression in oncogenes and HIV viral genes.