多功能集成的DNA纳米材料的构建及其作为mRNA疫苗载带佐剂平台的研究

mRNA疫苗是重大传染疾病免疫预防和癌症免疫治疗的一种新型疫苗，具有快速应对新冠病毒感染肺炎等突发性传染病的潜力。然而，mRNA疫苗的有效靶向递送和免疫激活性能调控一直是限制其临床应用研究的主要障碍。发展新型高效的mRNA疫苗载带平台是突破mRNA应用瓶颈的关键。本项目拟利用DNA分子的生物功能和精准组装优势，设计并构建集mRNA锚定模块、靶向模块、响应模块与佐剂模块为一体的多功能集成DNA纳米材料，并用作mRNA疫苗载带佐剂系统，同时实现mRNA疫苗的高效靶向递送、翻译效率可调和高效免疫共刺激等多种目标。首先，通过DNA分子设计，构建四大功能模块组装基元库；之后，通过精准组装和各大功能组装基元的比例调控，实现功能按需精准适配和mRNA疫苗的高效负载，构建多功能集成的DNA纳米材料；最后，在细胞水平和动物水平评估纳米载带佐剂系统的免疫激活性能。本项目拟为mRNA疫苗的临床应用奠定重要基础。

Messenger RNA (mRNA)-based vaccine has emerged as a promising and versatile platform to against infectious diseases and several types of cancer, and has the potential of quickly responding to sudden infectious diseases such as the coronavirus disease 2019 (COVID-19). However, their application has until recently been restricted by the inefficient in vivo delivery of mRNA and the regulation of immune activation. Development of a safe and effective delivery system for mRNA vaccine is highly desirable. The project intends to design and construct a multifunctional integrated DNA nanomaterial with four functional modules: mRNA anchoring module, targeting module, response module and adjuvant module. And then the multifunctional integrated DNA nanomaterial will be used as a carrier vehicle for mRNA vaccine, which is proposed to efficiently load and deliver mRNA vaccine, regulate translation efficiency to efficiently produce the interested proteins, and achieve efficient immuno-costimulating. The immune efficacy will be evaluated at a cellular level and in animals. This project intends to establish a general efficient mRNA delivery platform with multifunctional integrated DNA nanomaterials, and lays an important foundation for the clinical application of mRNA vaccine.