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[基于寡核苷酸的疗法作为一种潜在的新型药物疗法]

[Oligonucleotide-based therapy as a potential new pharmacotherapy].

作者信息

Morishita R

机构信息

Division of Gene Therapy Science, Osaka University Medical School, Suita-shi, Japan.

出版信息

Nihon Yakurigaku Zasshi. 2000 Mar;115(3):123-30. doi: 10.1254/fpj.115.123.

DOI:10.1254/fpj.115.123
PMID:10876797
Abstract

Recent progress in molecular biology has provided new techniques to inhibit target gene expression. Especially, the application of DNA technology such as antisense strategy to regulate the transcription of disease-related genes in vivo has important therapeutic potential. Recently, transfection of cis-element double-stranded (ds) oligodeoxynucleotides (ODN) (= decoy) as a powerful tool in a new class of anti-gene strategies for gene therapy and the study of transcriptional regulation has been reported. Transfection of ds ODN corresponding to cis sequence will result in the attenuation of authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements with subsequent modulation of gene expression. This "decoy" strategy is not only a novel strategy for gene therapy as an anti-gene strategy, but also a powerful tool for the study of endogenous gene regulation in vivo as well as in vitro. In this article, we reviewed 1) the mechanisms, and 2) potential applications of decoy strategy.

摘要

分子生物学的最新进展提供了抑制靶基因表达的新技术。特别是,诸如反义策略等DNA技术在体内调节疾病相关基因转录的应用具有重要的治疗潜力。最近,有报道称,作为一类新型的基因治疗和转录调控研究的抗基因策略中的一种强大工具,顺式元件双链(ds)寡脱氧核苷酸(ODN)(即诱饵)的转染已被报道。对应于顺式序列的ds ODN的转染将导致真实的顺式-反式相互作用减弱,从而使反式因子从内源性顺式元件上脱离,随后调节基因表达。这种“诱饵”策略不仅是一种作为抗基因策略的新型基因治疗策略,也是一种在体内和体外研究内源性基因调控的强大工具。在本文中,我们综述了:1)诱饵策略的机制;2)诱饵策略的潜在应用。

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