Aronsohn A I, Hughes J A
Department of Pharmaceutics, University of Florida, Gainesville 32610, USA.
J Drug Target. 1998;5(3):163-9. doi: 10.3109/10611869808995871.
The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems do not incorporate a mechanism for gene transport into the nucleus. Nuclear localization signal peptides can combine the increased expression of viral delivery systems with the safety and ease of preparation of non-viral delivery systems. A novel non-viral delivery vehicle consisting of a conglomerate of a synthetic nuclear localization signal peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a cationic lipid DOTAP:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian neuroblastoma cells. A three-fold increase in luciferase expression was seen with the delivery system containing a NLS peptide over cationic liposome controls. Examination of the factors that limit the rate of transgene expression can potentially lead to the discovery of new ways to improve the efficiency and efficacy of nonviral methods of gene therapy.
将基因用作治疗药物可能会涉及非病毒递送系统。虽然传统上非病毒递送系统在基因表达方面效果较差，但其优点包括易于生产、毒性较低且无感染风险。然而，大多数非病毒系统没有将基因转运到细胞核中的机制。核定位信号肽可以将病毒递送系统增加的表达与非病毒递送系统的安全性和制备简便性结合起来。一种新型非病毒递送载体由源自SV40病毒的合成核定位信号肽、编码荧光素酶的PGL3质粒和阳离子脂质DOTAP:DOPE（1:1 w/w）脂质体组成的聚集体构成，被转染到SKnSH哺乳动物神经母细胞瘤细胞中。与阳离子脂质体对照相比，含有核定位信号肽的递送系统使荧光素酶表达增加了三倍。对限制转基因表达速率的因素进行研究可能会发现提高非病毒基因治疗方法效率和效果的新途径。
