Nuclear localization signal peptides enhance cationic liposome-mediated gene therapy
Nuclear localization signal peptides enhance cationic liposome-mediated gene therapy
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DOI：
10.3109/10611869808995871
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发表时间：
1998-01-01
影响因子：
4.5
通讯作者：
Hughes, JA
中科院分区：
文献类型：
--
作者：
Aronsohn, AI;Hughes, JA
基因作为治疗药物的使用可能涉及非病毒递送系统，虽然传统上对基因表达不太有效，但非病毒递送系统的优点包括易于生产，毒性较低，并且没有感染的风险。然而，大多数非病毒系统不包括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的增加的表达与非病毒递送系统的安全性和制备的容易性结合联合收割机。将由衍生自SV 40病毒的合成核定位信号肽、编码荧光素酶的PGL 3质粒和阳离子脂质DOTAP：DOPE（1：1 w/w）脂质体的聚集体组成的新型非病毒递送载体转染到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，用含有NLS肽的递送系统观察到荧光素酶表达增加三倍。对限制转基因表达速率的因素的研究可能会导致发现新的方法来提高非病毒基因治疗方法的效率和功效。
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.