Editorials |
From the Department of Medicine, Brigham & Womens Hospital, Boston, Mass.
Correspondence to Victor J. Dzau, MD, Chairman, Department of Medicine, Brigham & Womens Hospital, Hersey Professor of Theory and Practice of Physic (Medicine), Harvard Medical School, 75 Francis St, Boston, MA 02115. E-mail vdzau@partners.org
Key Words: transcription regulation transcription factor decoy gene therapy molecular therapy
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Numerous studies have demonstrated the importance of altered gene expression in disease pathophysiology. Thus, modification of gene expression has emerged as an important therapeutic strategy.1 Agents that inhibit the transcription of disease-mediating genes or transactivate the expression of genes whose products disrupt pathophysiological processes are being developed. Regulation of gene expression is a complex biological process involving transcription factorDNA interaction that initiates gene transcription. Transcription factors are proteins residing in the cell nucleus or cytoplasm that upon activation bind with specific DNA motifs in the promoter region of the target gene. The activation process may involve phosphorylation, dimerization, proteolytic cleavage, ubiquitination, and/or translocation. Accordingly, molecules that block one or more steps of the transcription machinery can potentially modify the expression of a specific gene or group of genes, yielding a functional response(s).
It has been shown that short sequences of DNA containing the consensus binding site, even in the absence of surrounding DNA, can bind transcription protein in a highly specific manner. Indeed, such oligonucleotides have been used as radiolabeled probes for the detection and characterization of transcription factors (TFs) in electrophoretic mobility shift assays. Specific DNA sequences have been used successfully as "decoys" to bind specific TFs in cultured cells or in vivo, rendering the TFs incapable of subsequent binding to the promoter region of target genes.1 This approach has been shown to be effective in modulating gene expression in vitro and in vivo. Indeed, the use of transcription factor decoy (TFD) as a tool to study gene expression
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