Abstract：
Oligonucleotides are increasingly being used as a programmable connection material to assemble molecules and proteins in well-defined structures. For the application of such assemblies for in vivo diagnostics or therapeutics it is crucial that the oligonucleotides form highly stable, non-toxic, and non-immunogenic structures. Only few oligonucleotide derivatives fulfil all of these requirements. Here we report on the application of acyclic l-threoninol nucleic acid (aTNA) to form a four-way junction (4WJ) that is highly stable and enables facile assembly of components for in vivo treatment and imaging. The aTNA 4WJ is serum-stable, shows no non-targeted uptake or cytotoxicity, and invokes no innate immune response. As a proof of concept, we modify the 4WJ with a cancer-targeting and a serum half-life extension moiety and show the effect of these functionalized 4WJs in vitro and in vivo, respectively.
摘要：
寡核苷酸越来越多地用作可编程连接材料以在明确定义的结构中组装分子和蛋白质。对于这种组件在体内诊断或治疗中的应用，至关重要的是寡核苷酸形成高度稳定的寡核苷酸。无毒,和非免疫原性结构。只有少数寡核苷酸衍生物满足所有这些要求。在这里，我们报道了无环1-苏氨酸醇核酸（aTNA）形成四向连接（4WJ）的应用，该连接高度稳定并能够轻松组装用于体内治疗和成像的组件。aTNA4WJ是血清稳定的，没有显示非靶向摄取或细胞毒性，并且不引起先天免疫反应。作为概念的证明，我们用癌症靶向和血清半衰期延长部分修饰4WJ，并显示这些功能化的4WJ在体外和体内的作用，分别。
