Lee I K, Ahn J D, Kim H S, Park J Y, Lee K U
Department of Internal Medicine, Keimyung University School of Medicine, Taegu, Korea.
Curr Drug Targets. 2003 Nov;4(8):619-23. doi: 10.2174/1389450033490821.
Decoy oligodeoxynucleotides (ODN) that can reduce the trans-activity of transcription factors may be highly useful in gene therapy and the study of transcriptional regulation. Several different types of these double-stranded DNA decoys have been developed, including unmodified oligonucleotide duplexes, alphabeta-anomeric oligonucleotides, and oligonucleotide duplexes with methylphosphonate- and phosphorothioate-modified linkages. The latter ODNs have been particularly extensively studied but suffer from a number of limitations, including their insensitivity to polymerases, their lack of sequence specificity, and their tendency to activate immune responses. To resolve these problems, circular dumbbell (CD) double-stranded ODNs were developed. These CD ODNs are constructed by the circularization of the 3' and 5' ends of the oligonucleotides and enzymatic ligation. They exhibit high resistance to nucleases, are easily taken up by cells, and have a nontoxic unmodified backbone that resembles natural DNA. In this article, we review the method of constructing CD ODNs and their advantages compared to other modified ODNs for use as transcription decoys.
能够降低转录因子反式活性的诱饵寡脱氧核苷酸（ODN）在基因治疗和转录调控研究中可能非常有用。已经开发出几种不同类型的双链DNA诱饵，包括未修饰的寡核苷酸双链体、αβ异头寡核苷酸以及具有甲基膦酸酯和硫代磷酸酯修饰连接的寡核苷酸双链体。后一种ODN已经得到了特别广泛的研究，但存在许多局限性，包括它们对聚合酶不敏感、缺乏序列特异性以及激活免疫反应的倾向。为了解决这些问题，人们开发了环形哑铃（CD）双链ODN。这些CD ODN是通过寡核苷酸3'端和5'端的环化以及酶促连接构建而成的。它们对核酸酶具有高度抗性，容易被细胞摄取，并且具有类似于天然DNA的无毒未修饰主链。在本文中，我们综述了构建CD ODN的方法以及与用作转录诱饵的其他修饰ODN相比它们的优势。
