Harashima H, Shinohara Y, Kiwada H
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, 060-0812, Sapporo, Japan
Eur J Pharm Sci. 2001 Apr;13(1):85-9. doi: 10.1016/s0928-0987(00)00211-6.
The objective of this review is to summarize some of the critical barriers in gene delivery and recent progress in overcoming such barriers using non-viral carrier systems. Receptor-mediated endocytosis is generally considered to be a principal entering pathway. Therefore, endosomal escape is an essential step for achieving efficient transfection. The nuclear membrane is also a critical barrier in gene delivery and the application of the nuclear localization signal is discussed, based on recent strategies. It is essential to optimize the carrier system, in order to enhance the transfection ability equivalent to a viral system. The importance of developing an intracellular pharmacokinetic model of genes is emphasized in the optimization of non-viral carrier systems.
本综述的目的是总结基因递送中的一些关键障碍,以及使用非病毒载体系统克服这些障碍的最新进展。受体介导的内吞作用通常被认为是主要的进入途径。因此,内体逃逸是实现高效转染的关键步骤。核膜也是基因递送中的一个关键障碍,本文基于近期策略讨论了核定位信号的应用。优化载体系统以提高与病毒系统相当的转染能力至关重要。在非病毒载体系统的优化中,强调了建立基因细胞内药代动力学模型的重要性。