PMID: 15216908Jun 26, 2004Paper

New trends in the development of transcription factor decoy (TFD) pharmacotherapy

Current Drug Targets
Roberto Gambari

Abstract

Many recent published observations firmly demonstrate that one of the ways to study and artificially modulate gene expression at the transcriptional level is offered by the "transcription factor decoy" (TFD) strategy. This experimental approach is based on the competition for trans-acting factors between endogenous cis-elements present within regulatory regions of target genes and exogenously added DNA sequences (the DNA-based drug) mimicking the specific cis-elements. The objective of this molecular intervention is to cause a decrease of the interactions of trans-factors with the target genomic cis-elements, leading to alteration of transcription. The characterisation of the biological activity of the designed decoy molecules is routinely assessed by molecular technologies, such as electrophoretic mobility gel shift assay (EMSA), competitive DNase I footprinting, in vitro transcription. New advances in this field employ biospecific interaction analysis (BIA) based on surface plasmon resonance (SPR) and biosensor technology. With respect to the design of the decoy biomolecules, in addition to double-stranded DNA/DNA hybrids, cross-linking between two DNA molecules either via photocrosslinking or by the introduction of a covalen...Continue Reading

Citations

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