Paris-based biotechnology company Genset has reported in thecurrent issue of Nucleic Acids Research an efficient new way toinhibit gene expression.

Genset researchers showed that short circles of DNA twisted onthemselves in a "dumbbell" shape inhibited expression of atarget gene both in vitro and ex vivo at nanomolarconcentrations, while double-stranded oligonucleotides are onlyeffective in vitro.

The oligonucleotides are about 60 base pairs long and form adouble-stranded section in the middle with loops ofapproximately five base pairs at the ends.

They serve as decoys and bind transcription factor proteinsthat normally bind the chromosomal DNA prior to geneexpression. The presence of several copies of theseoligonucleotides efficiently competes with promoter orenhancer regions of chromosomal DNA for binding oftranscription factors, said Pascal Brandys, Genset's presidentand chief executive officer.

The looped ends, meanwhile, resist enzymatic degradation.

Genset has scaled up manufacture of these dumbbellcompounds and filed patent applications on them.

In another, contrasting approach, start-up company TularikInc. of South San Francisco, Calif., is focusing on using smallmolecules to control the activity of transcription factors.

-- Nancy Garcia Associate Editor

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