Development of Multifunctional Envelope type Nano Device based on Programmed Packaging

需要一个合理的策略来克服细胞和细胞内的障碍，并开发一种创新的非病毒基因传递系统。一种新的概念“程序化包装”，用于设计和组装智能纳米器件，使其成为一个集成的、独特的非病毒基因传递系统。基于这一概念，选择了细胞入口对于基因传递系统的重要性，使用Tf作为受体介导的内吞途径，而辛精氨酸作为非内吞途径。八精氨酸修饰的包膜型纳米装置证明了非内吞途径的优势，其转染活性与腺病毒一样高。最后，描述了基因传递系统的细胞内运输的三维定量分析及其在传递系统的药代动力学优化中的应用。这些新方法将最终导致一种非病毒基因传递系统的发展，这种系统不仅在安全性上优于病毒载体，而且在效率上也优于病毒载体。

A rational strategy is required to overcome cellular and intracellular barriers and to develop an innovative non-viral gene delivery system. A new concept "Programd Packaging", for the design and assembling of intelligent nano devices into an integrated, unique non-viral gene delivery system has been developed. Based on this concept, the importance of cellular entrance for a gene delivery system, using Tf as a receptor-mediated endocytic pathway and octaarginine as a non-endocytic pathway was chosen. The advantage of a non-endocytic pathway is demonstrated by an octaarginine-modified envelope type nano device, which exerts transfection activities as high as an adenovirus. Finally, a three dimensional quantitative assay for the intracellular trafficking of a gene delivery systems and its application for the pharmacokinetic optimization of a delivery system is described. These new approaches will ultimately lead to the development of a non-viral gene delivery system which is superior to viral vectors not only from the point of view of safety, but efficiency as well.