Design of systemic siRNA delivery system based on quantitative analyses of intracellular trafficking

在这项研究中，在体外和体内设置之间的比较分析进行了检查，以开发一个有效的体内核酸输送系统。我们专注于三个主要的细胞内运输过程：积累，内体逃逸，和组织或细胞中的去凝聚过程。我们发现，积累过程是在低剂量下实现体内核酸活性的关键因素。此外，通过改善细胞质中的核酸解凝聚过程来增加核酸活性。最后，我们通过使用体内核酸递送系统成功地预防了小鼠的急性肝肝炎和2型糖尿病和肥胖症的症状。

In this study, comparative analyses between in vitro and in vivo settings were examined in order to develop an efficient in vivo nucleic acid delivery system. We focused on three main intracellular trafficking processes; accumulation, endosome escape, and decondensation process in tissues or cells. We found that the accumulation process is a key factor in achieving in vivo nucleic acid activity at low dose. In addition, nucleic acid activity was increased by improving nucleic acid decondensation process in cytoplasm. Lastly, we have succeeded to prevent acute liver hepatitis and the symptoms of type 2 diabetes and obesity in mice by using the in vivo nucleic acid delivery system.