Tomita Naruya, Tomita Tetsuya, Yuyama Kazuhiko, Tougan Takahiro, Tajima Tsuyoshi, Ogihara Toshio, Morishita Ryuichi
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan.
Curr Opin Mol Ther. 2003 Apr;5(2):107-12.
The inhibition of specific transcription regulatory proteins is a novel approach to regulate gene expression. The transcriptional activities of DNA binding proteins can be inhibited by the use of double-stranded oligonucleotides (ODNs) that compete for binding to their specific target sequences in promoters and enhancers. Transfection of this cis-element double-stranded ODN, referred to as decoy ODN, has been reported to be a powerful tool that provides a new class of anti-gene strategies to gene therapy and permits examination of specific gene regulation. We have demonstrated the usefulness of this decoy ODN strategy in animal models of restenosis, myocardial infarction, glomerulonephritis and rheumatoid arthritis. However, one of the major limitations of decoy ODN technology is the rapid degradation of phosphodiester ODNs by intracellular nucleases. To date, several different types of double-stranded decoy ODNs have been developed to overcome this issue. Circular dumb-bell (CD) double-stranded decoy ODNs that were developed to resolve this issue have attracted a high level of interest. In this review, the applications of decoy ODN strategy and the advantages of modified CD double-stranded decoy ODNs will be discussed.
抑制特定转录调节蛋白是一种调控基因表达的新方法。通过使用双链寡核苷酸（ODN）可抑制DNA结合蛋白的转录活性，这些双链寡核苷酸能竞争结合启动子和增强子中的特定靶序列。据报道，转染这种顺式作用元件双链ODN（称为诱饵ODN）是一种强大的工具，为基因治疗提供了一类新的反基因策略，并可用于研究特定基因的调控。我们已经证明了这种诱饵ODN策略在再狭窄、心肌梗死、肾小球肾炎和类风湿性关节炎动物模型中的有效性。然而，诱饵ODN技术的主要局限性之一是磷酸二酯ODN会被细胞内核酶迅速降解。迄今为止，已开发出几种不同类型的双链诱饵ODN来克服这一问题。为解决此问题而开发的环状哑铃（CD）双链诱饵ODN引起了高度关注。在本综述中，将讨论诱饵ODN策略的应用以及修饰的CD双链诱饵ODN的优势。
