DNA origami is a powerful nanomaterial for biomedical applications due in part to its capacity for programmable, site-specific functionalization. To realize these applications, scalable and efficient conjugation protocols are needed for diverse moieties ranging from small molecules to biomacromolecules. Currently, there are no facile and general methods for in situ covalent modification and label-free quantification of reaction conversion. Here, we investigate the postassembly functionalization of DNA origami and the subsequent high-performance liquid chromatography-based characterization of these nanomaterials. Following this approach, we developed a versatile DNA origami functionalization and characterization platform. We observed quantitative in situ conversion using widely accessible click chemistry for carbohydrates, small molecules, peptides, polymers, and proteins. This platform should provide broader access to covalently functionalized DNA origami, as illustrated here by PEGylation for passivation and HIV antigen decoration to construct virus-like particle vaccines.

中文翻译：

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DNA折纸病毒样颗粒的原位共价功能化

DNA 折纸是一种用于生物医学应用的强大纳米材料，部分原因在于它具有可编程、特定位点功能化的能力。为了实现这些应用，从小分子到生物大分子的不同部分需要可扩展且高效的偶联方案。目前，对于反应转化的原位共价修饰和无标记定量还没有简便通用的方法。在这里，我们研究了 DNA 折纸的组装后功能化以及随后基于高效液相色谱法对这些纳米材料进行的表征。按照这种方法，我们开发了一个多功能的 DNA 折纸功能化和表征平台。我们在原位观察到定量使用广泛适用的点击化学对碳水化合物、小分子、肽、聚合物和蛋白质进行转换。该平台应提供更广泛的共价功能化 DNA 折纸，如用于钝化的聚乙二醇化和用于构建病毒样颗粒疫苗的 HIV 抗原修饰所示。