Kogure Kentaro, Akita Hidetaka, Harashima Hideyoshi
Kyoto Pharmaceutical University, Japan.
Yakugaku Zasshi. 2008 Feb;128(2):219-32. doi: 10.1248/yakushi.128.219.
Non-viral vectors need to overcome several barriers such as the plasma membrane, the endosomal membrane and the nuclear membrane for efficient gene delivery to the nucleus of target cells. To overcome these obstacles, the delivery system must be equipped with various functional devices. However, it is difficult to package all these needed devices into a single system to exert each of their functions at the appropriate time and at the correct location. Thus, our group proposed a new packaging concept, "Programmed Packaging". A multifunctional envelope-type nano device (MEND) was developed for use as an efficient non-viral system for the delivery of plasmid DNA (pDNA), oligodeoxynucleotide (ODN) and siRNA. Various types of MEND were developed as to strategy and situations. For example, the octaarginine (R8)-modified MEND (R8-MEND) encapsulating pDNA showed significantly high transfection activity comparable to adenovirus, and the up-take pathway of the R8-MEND was macropinocytosis, which can avoid lysosomal degradation. The R8-MEND successfully delivered a gene to hair follicles of mouse skin by in vivo topical application. Consequently, our group succeeded in the development of the MEND based on the Programmed Packaging, and found this to be a promising new delivery system of pDNA and functional nucleic acids.
非病毒载体需要克服诸如质膜、内体膜和核膜等多种障碍，才能将基因有效地递送至靶细胞的细胞核。为了克服这些障碍，递送系统必须配备各种功能装置。然而，很难将所有这些所需的装置整合到一个单一系统中，以便在适当的时间和正确的位置发挥各自的功能。因此，我们团队提出了一种新的包装概念——“程序化包装”。开发了一种多功能包膜型纳米装置（MEND），用作递送质粒DNA（pDNA）、寡脱氧核苷酸（ODN）和小干扰RNA（siRNA）的高效非病毒系统。根据策略和应用场景开发了多种类型的MEND。例如，包裹pDNA的八聚精氨酸（R8）修饰的MEND（R8-MEND）表现出与腺病毒相当的显著高转染活性，并且R8-MEND的摄取途径是巨胞饮作用，这可以避免溶酶体降解。通过体内局部应用，R8-MEND成功地将基因递送至小鼠皮肤的毛囊。因此，我们团队成功开发了基于程序化包装的MEND，并发现这是一种有前景的pDNA和功能性核酸新递送系统。
