Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Application of Decoy Oligodeoxynucleotides-Based Approach to Renal Diseases

Author(s): Naruya Tomita, Haruhito Azuma, Yasufumi Kaneda, Toshio Ogihara, Ryuichi Morishita.

Abstract:

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.

Keywords: transcription factor decoy, glomerulonephritis, renal transpantation, hvj-liposome

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Article Details

VOLUME: 5
ISSUE: 8
Year: 2004
Page: [717 - 733]
Pages: 17
DOI: 10.2174/1389450043345146
Price: $58