基于多肽/DNA超分子组装构筑的人工病毒及其应用

病毒是衣壳蛋白和核酸之间通过非共价相互作用形成的超分子组装结构，模拟其结构进行人工病毒的构筑是认识病毒作用机制和发展非病毒载体的重要途径，具有重要的理论意义和应用价值。本项目拟开展“基于多肽/DNA超分子组装构筑的人工病毒及其应用”研究，通过合理的分子设计调控多肽的自组装行为，形成模拟衣壳蛋白结构特征的组装基元，然后与DNA共组装构筑人工病毒，考察其在基因转染和治疗中的应用，同时将荧光基团引入人工病毒，实现基因治疗和自我示踪功能的集成。项目研究将建立多肽分子设计的指导性原则，获得简单高效且易于大量制备的肽分子体系，通过多肽/核酸的超分子组装获得结构高度规整的人工病毒，突破当前分子组装体系难以实现高仿真病毒结构模拟的瓶颈。此类人工病毒不仅在组成、结构和功能等各个方面都接近于天然病毒，而且有可设计性强、结构动态可控、生物相容性高、易于功能化等优点，有望实现智能、高效的基因治疗作用。

Natural viruses can be taken as supramolecular assemblies formed by capsid proteins and nucleic acids via various non-covalent interactions. To construct the artificial viruses by mimicking the virus’ supramolecular assembly is an important strategy to probe into their functional mechanisms as well as to develop non-viral gene vectors, which is of great significance in both theoretical aspect and practical applications. The current project proposes the study of ‘Fabrication of Artificial Viruses from the Peptide/DNA Supramolecular Assembly and Their Applications’. We will firstly design peptides with varied molecular structures, controlling their self-assembling behaviors to form self-assembled structures that mimic well the capsid protein structural characteristics. Then the artificial viruses will be constructed from the peptide/DNA co-assembly. We will further our study to apply the artificial viruses in gene transfection and gene therapy. Simultaneously we will introduce fluorophores into the artificial viruses so as to realize the integrated function of gene therapy and self-tracing. The project will establish the guiding rules for peptide molecular design and obtain simple, efficient and versatile molecular systems that can interact with nucleic acids via supramolecular assembly to form artificial viruses with high structural regularity and stability. It will lead to a breakthrough in mimicking the virus’ structural characteristics by molecular self-assembly. The peptide/DNA supramolecular assemblies can not only mimic well the natural viruses from the aspects of composition, structure and function, but also have advantages of easy design, dynamic and controllable structures, high biocompatibility, and ready for functioning. Therefore, they are hopefully to realize smart and efficient gene therapeutic effect.