Recent advances in synthetic biology have led to the development of nucleic acid polymers with backbone structures distinct from those found in nature, termed xeno-nucleic acids (XNAs). Several unique properties of XNAs make them attractive as nucleic acid therapeutics, most notably their high resistance to serum nucleases and ability to form Watson-Crick base pairing with DNA and RNA. The ability of XNAs to induce immune responses has not been investigated. Threose nucleic acid (TNA), a type of XNA, is recalcitrant to nuclease digestion and capable of undergoing Darwinian evolution to produce high affinity aptamers; thus, TNA is an attractive candidate for diverse applications, including nucleic acid therapeutics. In this study, we evaluated a TNA oligonucleotide derived from a cytosine-phosphate-guanine oligonucleotide sequence known to activate toll-like receptor 9-dependent immune signaling in B cell lines. We observed a slight induction of relevant mRNA signals, robust B cell line activation, and negligible effects on cellular proliferation.

中文翻译：

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完全由苏糖核酸组成的CpG寡核苷酸序列激活先天免疫应答。

合成生物学的最新进展已导致开发了具有不同于自然界中发现的骨架结构的核酸聚合物，称为异种核酸（XNA）。XNA的几个独特特性使其成为核酸治疗剂具有吸引力，最著名的是它们对血清核酸酶的高抗性以及与DNA和RNA形成Watson-Crick碱基配对的能力。XNA诱导免疫反应的能力尚未研究。苏糖核酸（TNA）是XNA的一种，对核酸酶消化具有顽固性，能够经历达尔文进化以产生高亲和力的适体；因此，TNA是包括核酸治疗剂在内的多种应用的有吸引力的候选者。在这个研究中，我们评估了一种TNA寡核苷酸，该寡核苷酸衍生自已知能激活B细胞系中Toll样受体9依赖性免疫信号转导的胞嘧啶-磷酸-鸟嘌呤寡核苷酸序列。我们观察到了相关mRNA信号的轻微诱导，强大的B细胞系激活以及对细胞增殖的影响可忽略不计。