Ziello Jennifer E, Huang Yan, Jovin Ion S
Boyer Center for Molecular Medicine, Yale University, New Haven, Connecticut, United States of America.
Mol Med. 2010 May-Jun;16(5-6):222-9. doi: 10.2119/molmed.2009.00101. Epub 2010 Feb 3.
Endocytosis is the process by which cells take up macromolecules from the surrounding medium. The best-characterized process is the so-called clathrin-dependent endocytosis, although much is also currently known about clathrin-independent endocytic processes such as those involving caveolae and lipid rafts. An understanding of endocytosis and the cellular trafficking that occurs thereafter has a great deal of relevance to current molecular medicine. Gene therapy, which is presently being investigated for its therapeutic potential in treating immunodeficiency and metabolic diseases, cancer and heart disease, employs a variety of viral and nonviral vectors, which can be delivered to the target cells of the body and are subsequently endocytosed and dissembled. A variety of vectors can be used to deliver genes to organs in vivo or cells ex vivo. Various routes of vector delivery have been investigated. The mechanisms by which vectors such as adenoviruses, adeno-associated viruses, retroviruses and liposomes enter the cell are increasingly being investigated as the effort to increase the efficiency of gene therapy continues. This review focuses on mechanisms of endocytosis and how they relate to the internal trafficking of viral and nonviral vectors in gene therapy.
内吞作用是细胞从周围介质中摄取大分子的过程。目前研究最充分的过程是所谓的网格蛋白依赖性内吞作用，不过目前对于非网格蛋白依赖性内吞过程，如涉及小窝和脂筏的过程也有很多了解。对内吞作用及其后续发生的细胞运输的理解与当前的分子医学密切相关。基因治疗目前正在研究其在治疗免疫缺陷、代谢疾病、癌症和心脏病方面的治疗潜力，它采用多种病毒和非病毒载体，这些载体可以递送至体内的靶细胞，随后被内吞并分解。多种载体可用于在体内将基因递送至器官或在体外递送至细胞。已经研究了多种载体递送途径。随着提高基因治疗效率的努力不断推进，腺病毒、腺相关病毒、逆转录病毒和脂质体等载体进入细胞的机制越来越受到研究。本综述重点关注内吞作用机制以及它们与基因治疗中病毒和非病毒载体的内部运输的关系。
