Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
Int J Pharm. 2018 Jun 10;544(1):39-45. doi: 10.1016/j.ijpharm.2018.04.015. Epub 2018 Apr 11.
Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR) modules, was employed as a targeting moiety. A polyanionic peptide was genetically fused to the repebody, followed by incubation with an HR-dendrimer and a DNA cargo to assemble the dendrimer complex through an electrostatic interaction. The resulting dendrimer complex was shown to deliver a DNA cargo with high efficiency in a receptor-specific manner. An analysis using a confocal microscope confirmed the internalization of the dendrimer complex and subsequent dissociation of a DNA cargo from the complex. The present approach can be broadly used in a targeted gene delivery in many areas.
虽然已经开发出了多种非病毒基因传递系统，但它们仍然存在效率和特异性低的问题。在此，我们提出了一种树状聚合物复合物的组装，该复合物由 DNA 货物和靶向部分组成，作为靶向基因传递的新形式。用组氨酸和精氨酸修饰的 PAMAM 树状聚合物（HR-树状聚合物）被用于增强内涵体逃逸和转染效率。表皮生长因子受体特异性的重复体，由富含亮氨酸的重复模块组成，被用作靶向部分。一个聚阴离子肽被遗传融合到重复体上，然后与 HR-树状聚合物和 DNA 货物孵育，通过静电相互作用组装成树状聚合物复合物。结果表明，该树状聚合物复合物以受体特异性的方式高效传递 DNA 货物。使用共聚焦显微镜进行的分析证实了树状聚合物复合物的内化以及随后 DNA 货物从复合物中的解离。本方法可广泛应用于许多领域的靶向基因传递。
