In vivo transcription of a progesterone-responsive gene is specifically inhibited by a triplex-forming oligonucleotide. Academic Article uri icon


  • Oligonucleotides provide novel reagents for inhibition of gene expression because of their high affinity binding to specific nucleotide sequences. We describe a 38 base, single-stranded DNA that forms a triple helix or 'triplex' on progesterone response elements of a target gene. This triplex-forming oligonucleotide binds with a Kd = 100 nM at 37 degrees C and physiological pH, and blocks binding of progesterone receptors to the target. Furthermore, it completely inhibited progesterone receptor-dependent transcription in vitro. To approach in vivo conditions, triplex-forming oligonucleotides were tested in cell transfection studies. The derivation of the oligonucleotides with cholesterol enhanced their cellular uptake and nuclear concentration by at least four-fold. The cholesterol-derivatized triplex-forming oligonucleotide specifically inhibited transcription of the PRE-containing reporter gene in cells when applied to the medium at micromolar concentrations. This is the first demonstration of steroid-responsive gene inhibition by triplex formation and joins the growing body of evidence indicating that oligonucleotides have therapeutic potential.

published proceedings

  • Nucleic Acids Res

altmetric score

  • 3

author list (cited authors)

  • Ing, N. H., Beekman, J. M., Kessler, D. J., Murphy, M., Jayaraman, K., Zendegui, J. G., ... Tsai, M. J.

citation count

  • 97

complete list of authors

  • Ing, NH||Beekman, JM||Kessler, DJ||Murphy, M||Jayaraman, K||Zendegui, JG||Hogan, ME||O'Malley, BW||Tsai, MJ

publication date

  • June 1993