Kogure Kentaro, Akita Hidetaka, Yamada Yuma, Harashima Hideyoshi
Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Adv Drug Deliv Rev. 2008 Mar 1;60(4-5):559-71. doi: 10.1016/j.addr.2007.10.007. Epub 2007 Oct 25.
In this review, we describe a key role of octaarginine (R8) in developing our new concept of "Programmed Packaging", by which we succeeded in creating a multifunctional envelope-type nano device (MEND) as a non-viral gene-delivery system. This concept can be applied not only to nuclear targeting of plasmid DNA (pDNA) but also to cytosolic delivery of functional nucleic acids such as oligonucleotides or siRNA. This concept has been extended to other organelles such as mitochondria as a foundation for innovative nanomedicine. Finally, we discuss the rate-limiting step in gene delivery by comparing non-viral and viral gene delivery systems, which clearly indicates the importance of nuclear disposition of pDNA for efficient transfection.
在本综述中，我们描述了八聚精氨酸（R8）在发展我们的“程序化包装”新概念中的关键作用，通过这一概念，我们成功创建了一种多功能包膜型纳米装置（MEND）作为非病毒基因递送系统。这一概念不仅可应用于质粒DNA（pDNA）的核靶向，还可应用于功能性核酸如寡核苷酸或siRNA的胞质递送。这一概念已扩展到其他细胞器如线粒体，作为创新纳米医学的基础。最后，我们通过比较非病毒和病毒基因递送系统来讨论基因递送中的限速步骤，这清楚地表明了pDNA的核定位对于有效转染的重要性。
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