The c-myc oncogene is one of the most commonly malfunctioning genes in
human cancers, and is an attractive target for anti-gene therapy. Alt
hough synthetic oligonucleotides designed to silence c-myc expression
via one of its major control elements function well in vitro, their mo
de of action has been indefinite, Here we show that the targeted contr
ol element adopts an intrastrand fold-back DNA tetraplex, which requir
es potassium ions for stability in vitro. We believe formation of the
tetraplex is important for c-myc activation in vivo, and propose a tra
nscription initiation mechanism that explains how anti-gene therapy si
lence c-myc at the molecular level.