J Biomed Nanotechnol. 2014 Jan;10(1):67-80. doi: 10.1166/jbn.2014.1682.
Non-viral carriers, able to regulate cellular uptake pathways are becoming promising vectors for efficient gene transfer into cells because the intracellular processing of gene is strongly determined by the internalization pathways and subsequent intracellular routes. The intracellular processing of gene can be directed either to digestive or non-digestive way depending on the endocytosis mechanism. Enormous attempts have been made to bypass or avoid the digestive way of lysosomal degradation for meaningful delivery of therapeutic genes at the target site. This review describes an updated information regarding regulation of endocytosis pathways in consequence with the cellular trafficking and the determinant factors of the initial mode of internalization route for rational design of non-viral gene carriers. Firstly, we describe various nonviral gene vectors and the key barriers to non-viral gene transfer. Secondly, various major endocytosis pathways and their significance in developing non-viral gene carriers are discussed. Thirdly, various factors that potentially regulate endocytosis pathways of gene carriers to improve gene delivery efficacy are elaborately described. Lastly, the perspectives of future studies to control endocytosis mechanisms are discussed to design potential non-viral gene vectors for active application in future.
非病毒载体能够调节细胞摄取途径,成为将基因高效转入细胞的有前途的载体,因为基因的细胞内处理强烈取决于内化途径和随后的细胞内途径。根据内吞作用机制,基因的细胞内处理可以定向到消化或非消化途径。已经进行了大量的尝试来绕过或避免溶酶体降解的消化途径,以在靶部位有意义地递送达治疗基因。本文综述了有关细胞内运输过程中内吞作用途径的调节以及初始内化途径的决定因素的最新信息,这对于合理设计非病毒基因载体具有重要意义。首先,我们描述了各种非病毒基因载体和非病毒基因转移的关键障碍。其次,讨论了各种主要的内吞作用途径及其在开发非病毒基因载体中的意义。第三,详细描述了可以调节基因载体的内吞作用途径以提高基因传递效率的各种因素。最后,讨论了控制内吞作用机制的未来研究的展望,以设计有潜力的非病毒基因载体,为未来的积极应用做好准备。