Abstract
A potential new therapeutic approach to control gene expression is the use of double-stranded (ds) oligodeoxyribonucleotides (oligos) to compete for the binding of nuclear factors to specific promoter and enhancer elements. As a model, we have tested the effect of oligo length, sequence and number of nuclear factor binding sites on in vitro transcription of adenovirus (Ad) Elb. Short ds oligos containing an SPI-binding sequence ( spl) inhibited transcription of Elb by more than 90%. Oligos containing multiple spl sequences were more effective inhibitors than would be expected for a comparable number of unlinked spl sites. A ds oligo with phosphorothioate (PS) linkages inhibited transcription at one-tenth the concentration needed for its normal homologue. An oligo with spl and a consensus TATA site was no more effective than one with spl alone. The stability of the PS-linked oligos will allow testing of this approach in vivo if they are adequately corporated into whole cells.
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