Geometrically-controlled self-assembly of synthetic molecular capsids

病毒是一种小的生物颗粒，由位于称为衣壳的分子外壳中的基于核酸的遗传信息组成。通常非常复杂的衣壳如何自我组装是一个迷人的研究领域，有许多未解之谜。在本项目中，天然病毒衣壳将作为构建合成分子衣壳的蓝图。我们将适应天然病毒衣壳的对称性，我们将利用准等效原理。在此基础上，我们将在cryo-EM结构分析指导下的迭代过程中设计基于DNA折纸的分子构建块的几何形状，以便这些组件可以有效地自组装成具有预定三角测量数的封闭衣壳。我们将实时监测衣壳的形成，并确定衣壳相相图作为环境条件的函数，以验证衣壳形成的理论预测。通过人工衣壳，除了对病毒衣壳组装原理的基本了解外，我们还旨在为未来用于药物和基因递送的先进合成载体奠定基础。

A virus is a small biological particle that consists of nucleic acid-based genetic information in a molecular shell called capsid. How the often very complex capsids self-assemble is a fascinating field of research with many unanswered questions. For the present project, natural virus capsids will serve as a blueprint for the construction of synthetic molecular capsids. We will adapt the symmetry properties of natural viral capsids and we will exploit the principle of quasi-equivalence. Based on this, we will design the geometry of DNA origami-based molecular building blocks in an iterative process guided by cryo-EM structural analysis so that these components can efficiently self-assemble into closed capsids with predetermined triangulation numbers. We will monitor capsid formation in real-time and determine a capsid-phase phase diagram as a function of environmental conditions to verify theoretical predictions of capsid formation. With the artificial capsids, in addition to basic insights into principles of viral capsid assembly, we also aim to lay the groundwork for future advanced synthetic vectors for drug and gene delivery.