Use of cyclic double-stranded oligonucleotides to inhibit gene expression

Abstract

Use of cyclic double-stranded oligonucleotides containing the binding site for a transcription factor for inhibiting gene expression are disclosed. The inventors propose use of double-stranded oligonucleotides to block DNA attachment of specific transcription factors thereby preventing expression of genes dependent on this transcription factor interaction. Oligonucleotides to HNF-1 transcription factor are used and it is demonstrated that such treatment leads to a block of expression of several liver specific genes under in vitro conditions. The closed oligonucleotides may be used to down-regulate the expression of genes such as fibrinogen and thus may be used for the treatment of coronary heart disease.