Medina-Kauwe L K, Xie J, Hamm-Alvarez S
Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Gene Ther. 2005 Dec;12(24):1734-51. doi: 10.1038/sj.gt.3302592.
Nonviral vectors continue to be attractive alternatives to viruses due to their low toxicity and immunogenicity, lack of pathogenicity, and ease of pharmacologic production. However, nonviral vectors also continue to suffer from relatively low levels of gene transfer compared to viruses, thus the drive to improve these vectors continues. Many studies on vector-cell interactions have reported that nonviral vectors bind and enter cells efficiently, but yield low gene expression, thus directing our attention to the intracellular trafficking of these vectors to understand where the obstacles occur. Here, we will review nonviral vector trafficking pathways, which will be considered here as the steps from cell binding to nuclear delivery. Studies on the intracellular trafficking of nonviral vectors has given us valuable insights into the barriers these vectors must overcome to mediate efficient gene transfer. Importantly, we will highlight the different approaches used by researchers to overcome certain trafficking barriers to gene transfer, many of which incorporate components from biological systems that have naturally evolved the capacity to overcome such obstacles. The tools used to study trafficking pathways will also be discussed.
由于非病毒载体具有低毒性和免疫原性、无致病性以及易于进行药物生产等特点，它们仍然是病毒的有吸引力的替代物。然而，与病毒相比，非病毒载体的基因转移水平仍然相对较低，因此改进这些载体的努力仍在继续。许多关于载体-细胞相互作用的研究报告称，非病毒载体能有效结合并进入细胞，但基因表达水平较低，因此引导我们关注这些载体的细胞内运输过程，以了解障碍出现在何处。在这里，我们将综述非病毒载体的运输途径，这里将其视为从细胞结合到细胞核递送的步骤。对非病毒载体细胞内运输的研究为我们提供了宝贵的见解，让我们了解这些载体为介导高效基因转移必须克服的障碍。重要的是，我们将强调研究人员用于克服某些基因转移运输障碍的不同方法，其中许多方法都纳入了来自生物系统的成分，这些生物系统自然进化出了克服此类障碍的能力。还将讨论用于研究运输途径的工具。
