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Application of Decoy Oligodeoxynucleotides-Based Approach to Renal Diseases

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Recent progress in cellular and molecular research has provided a new technique to inhibit target gene expression based on DNA technology such as antisense oligodeoxynucleotides (ODN), small interfering RNA (siRNA), ribozyme and decoy ODN. Especially, recently, a successful ODN-based approach termed decoy ODN has used synthetic ODN containing an enhancer element that can penetrate cells, to bind to sequence-specific DNA-binding proteins and interfere with transcription in vitro and in vivo. Transfer of cis-element double-stranded decoy ODN has been reported as a new powerful tool in a new class of anti-gene strategies to treat various diseases as gene therapy or as a research tool to examine the molecular mechanisms of expression of a specific gene. Transfer of double-stranded ODN corresponding to the cis-sequence will result in attenuation of the authentic cis-trans interaction, leading to removal of trans-factors from the endogenous cis-elements with subsequent modulation of gene expression. To date, we have chosen several target transcription factors such as nuclear factor-κB (NF-κB) and E2F to prevent the progression of several diseases including renal diseases. As other targets, we focused on negative regulatory element (NRE) for the renin gene and angiotensinogen gene-activating element (AGE) for the angiotensinogen gene to examine the molecular mechanisms of gene expression, AP-1 and ets-1. In this paper, we introduce the decoy strategy and demonstrate examples of application of decoy ODN approach targeting E2F and NF-κB in renal diseases.
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Keywords: glomerulonephritis; hvj-liposome; renal transpantation; transcription factor decoy

Document Type: Review Article

Affiliations: Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.

Publication date: November 1, 2004

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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