Geometrically-controlled self-assembly of synthetic molecular capsids

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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.