Single-strand oligodeoxynucleotides (ODNs) containing unmethylated cytosine-phosphate-guanine (CpG) are recognized by the toll-like receptor 9, a component of the innate immunity. Therefore, they could act as immunotherapeutic agents. Chemically modified CpG ODNs containing a phosphorothioate backbone instead of phosphodiester (PD) were developed as immunotherapeutic agents resistant to nuclease degradation. However, they cause adverse side effects, and so there is a necessity to generate novel CpG ODNs. In the present study, we designed a nuclease-resistant nonmodified CpG ODN that forms G-quadruplex structures. G-quadruplex formation in CpG ODNs increased nuclease resistance and cellular uptake. The CpG ODNs designed in this study induced interleukin-6 production in a human B lymphocyte cell line and human peripheral blood mononuclear cells. These results indicate that G-quadruplex formation can be used to increase the immunostimulatory activity of CpG ODNs having a natural PD backbone.

中文翻译：

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G四联体结构改善CpG寡核苷酸的免疫刺激作用。

包含未甲基化的胞嘧啶-磷酸-鸟嘌呤（CpG）的单链寡脱氧核苷酸（ODN）被先天免疫的组成部分toll样受体9识别。因此，它们可以充当免疫治疗剂。已开发了包含硫代磷酸酯骨架而不是磷酸二酯（PD）的化学修饰的CpG ODN作为抗核酸酶降解的免疫治疗剂。但是，它们会引起不利的副作用，因此有必要生成新的CpG ODN。在本研究中，我们设计了形成G-四链体结构的耐核酸酶的未修饰CpG ODN。CpG ODN中的G-四链体形成增加了核酸酶抗性和细胞摄取。在这项研究中设计的CpG ODN诱导人B淋巴细胞细胞系和人外周血单核细胞中白介素6的产生。