Application of decoy oligodeoxynucleotides-based approach to renal diseases.
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-kappaB (NF-kappaB) 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-kappaB in renal diseases.
Tomita
Naruya
N
Division of Clinical Gene Therapy, Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan. tomita@hp-gm.med.osaka-u.ac.jp
Azuma
Haruhito
H
Kaneda
Yasufumi
Y
Ogihara
Toshio
T
Morishita
Ryuichi
R
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050684:E2F Transcription Factors; D015316:Genetic Therapy / Q000379:methods*; D005921:Glomerulonephritis / Q000628:therapy; D006801:Humans; D007674:Kidney Diseases / Q000628:therapy*; D016030:Kidney Transplantation; D016328:NF-kappa B / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D014157:Transcription Factors / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors