Development of Multifunctional Envelope type Nano Device based on Programmed Packaging

基于程控封装的多功能封套型纳米器件的研制

• 批准号: 15300151
• 负责人: HARASHIMA Hideyoshi
• 金额: $ 11.07万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15300151/
• 关键词: gene delivery system; endocytosis; octaarginin; programmed packaging; MEND; アデノウイルス; 非ウイルスベクター; 定量的評価

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.

需要一个合理的策略来克服细胞和细胞内的障碍，并开发一个创新的非病毒基因传递系统。一个新的概念“程序化包装”，用于设计和组装智能纳米器件到一个集成的，独特的非病毒基因传递系统已经开发出来。基于这一概念，选择了细胞入口对于基因递送系统的重要性，使用Tf作为受体介导的内吞途径和八精氨酸作为非内吞途径。非内吞途径的优点通过辛托溴铵修饰的包膜型纳米装置证明，其发挥与腺病毒一样高的转染活性。最后，一个三维定量分析的细胞内运输的基因传递系统和其应用的药物动力学优化的传递系统进行了说明。这些新方法将最终导致非病毒基因递送系统的发展，该系统不仅从安全性的角度来看，而且从效率的角度来看，都上级病毒载体。

项目成果

リポソーム封入物質がエンドソームから脱出可能なリポソーム

脂质体，其中脂质体包封的物质可以从内涵体中逸出

• 发表时间: 2004

細胞に導入した核酸の標的オルガネラにおける局在量を定量する方法

用于定量引入靶细胞器中的细胞中的定位核酸的量的方法

• 发表时间: 2003

Factors governing the in vivo tissue uptake of transferrin-coupled polyethylene glycol liposomes in vivo

• DOI: 10.1016/j.ijpharm.2004.05.025
• 发表时间: 2004-08-20
• 期刊: INTERNATIONAL JOURNAL OF PHARMACEUTICS
• 影响因子: 5.8
• 作者: Hatakeyama, H;Akita, H;Harashima, H
• 通讯作者: Harashima, H

H.Akita: "Quantitative three-dimesional analysis of theintracellular trafficking of plasmid DNA transfected by non-viral gene delivery system using confocal laser"Mol.Ther.. 9. 443-451 (2004)

H.Akita：“使用共焦激光对非病毒基因传递系统转染的质粒 DNA 的细胞内运输进行定量三维分析”Mol.Ther.. 9. 443-451 (2004)

Quantitative three-dimesional analysis of the intracellular trafficking of plasmid DNA transfected by non-viral gene delivery system using confocal laser scanning microscopy.

使用共焦激光扫描显微镜对非病毒基因传递系统转染的质粒 DNA 的细胞内运输进行定量三维分析。

• 发表时间: 2004
• 期刊: Mol.Ther. 9
• 作者: U.Hasegawa;S.M.Nomura;S.C.Kaul;T.Hirano;K.Akiyoshi;H.Akita
• 通讯作者: H.Akita