流感病毒严重威胁人类健康，能感染广泛宿主，每年全球约6亿人感染，导致数十万人死亡。利用非天然基因编码技术改造流感病毒有望为病毒感染分子机制研究、新型病毒疫苗创制提供全新的研究工具。具备优良生物正交性和复制/转录效率的人造基因密码是非天然基因编码技术的关键化学基础。本项目团队成员合成了迄今活性最高的人造碱基对TPT3-NaM，有望作为非天然基因密码用于人工改造流感病毒。将TPT3-NaM核苷酸有效转运至宿主细胞是其应用的前提及关键科学问题。本项目拟利用前药策略构建TPT3-NaM核苷酸输送系统。采用已成功用于核苷酸类前药如索非布韦等的转运基团修饰TPT3-NaM核苷酸合成系列前药并研究其跨膜活性，筛选高效地转运并在细胞内代谢释放出TPT3-NaM核苷酸的前药分子。该项目的实施，有望为阐释流感病毒在宿主细胞中复制分子机制提供全新的生物学工具，为新型流感病毒疫苗的开发提供方法学基础

Influenza virus is one of the major threats to human health, which can infect a wide range of hosts. Seasonal epidemics cause about 600 million people infected worldwide annually, and lead to the death of 250-500 thousand people. The use of gene coding technique for modifications of influenza viruses is a promising approach for researches on the mechanisms of viral infections and manufactures of new virus vaccines. The efficiency and fidelity of artificial genetic code is the key for the development of the new gene coding techniques. Recently, we synthesized an artificial TPT3-NaM base pair, which was found as the most effective artificial genetic code so far. TPT3-NaM base pair is expected to be used for the construction of artificial influenza virus based on the modifications of virus gene with TPT3-NaM as unnatural base pair. This project aims to construct a new delivery system of this kind of artificial base pair TPT3-NaM and an evaluation system for the retention efficiency of the unnatural base pairs after transfections in vivo. This will supply a useful chemical biological tool for the investigation of virus duplications in host cells and offer new methodologies for the development of influenza virus vaccines.