Therapeutic applications of transcription factor decoy oligonucleotides.

Abstract

As alterations in gene expression have become a better understood component of normal development and disease pathogenesis, transcription factors and other regulators of gene expression have become an increasingly attractive target for potential therapeutic intervention. Transcription factors are generally nuclear proteins that play a critical role in gene regulation and can exert either a positive or negative effect on gene expression. These regulatory proteins bind specific sequences found in the promoter regions of their target genes. These binding sequences are generally 6–10 bp in length and are occasionally found in multiple iterations. Although this protein-DNA interaction is quite sequence-specific, the binding sites for a single transcription factor may vary by several base pairs when found in the promoter regions of different genes; in this case, a common motif, or consensus binding site, can be described. Often a number of different transcription factor binding sites are located in the regions both upstream and downstream from a given transcription initiation site. The binding of these different factors, and the subsequent interactions of these proteins with each other, as well as with RNA polymerases or their cofactors, yield a complex set of conditions that determines the relative transcriptional activity at different times and under varying conditions in different cell types.