Geometrically-controlled self-assembly of synthetic molecular capsids

合成分子衣壳的几何控制自组装

• 批准号: 422408755
• 负责人: Professor Dr. Hendrik Dietz
• 金额: --
• 依托单位: Arbeitsgruppe Biomolekulare Nanotechnologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/422408755?language=en
• 关键词: Geometrically; controlled; self; assembly; synthetic

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.

病毒是一种小的生物颗粒，由一个叫做衣壳的分子壳中的核酸遗传信息组成。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，有许多悬而未决的问题。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。我们将采用天然病毒衣壳的对称性，并利用拟等价原理。在此基础上，我们将在低温电镜结构分析的指导下，在迭代过程中设计基于DNA折纸的分子构建块的几何形状，使这些组件能够有效地自组装成具有预定三角数的封闭衣壳。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。利用人工衣壳，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传递的高级合成载体奠定基础。