A multifunctional envelope-type nano device for novel gene delivery of siRNA plasmids
A multifunctional envelope-type nano device for novel gene delivery of siRNA plasmids
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DOI：
10.1016/j.ijpharm.2005.05.021
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发表时间：
2005-09-14
影响因子：
5.8
通讯作者：
Harashima, H
中科院分区：
文献类型：
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作者：
Moriguchi, R;Kogure, K;Harashima, H
描述了用于递送siRNA表达质粒的多功能包膜型纳米装置（MEND）。将编码抗荧光素酶短干扰RNA （siRNA）的质粒DNA用聚l -赖氨酸（PLL）浓缩后装入MEND中。在一项共转染研究中，MEND（PLL）的沉默效应显示对荧光素酶活性的抑制率为96%。即使在100倍稀释条件下，沉默效果仍保持在60%以上。然而，在荧光素酶转化的细胞中，MEND（PLL）没有表现出显著的沉默作用（10%），这表明MEND（PLL）转染的异质性。为了解决这一问题，通过比较PLL、硬脂酰辛精氨酸（STR-R8）和鱼精蛋白（Prot）对DNA凝聚剂进行优化。在一项共转染研究中，这些MENDs的沉默效应没有差异（95-97%）。然而，在转化的细胞中，MEND（Prot）显示出70%的沉默效应。这些结果表明，MEND（Prot）的转染异质性较小，而MEND（PLL）和MEND（STR-R8）的转染异质性较大。这些结果表明，MEND（Prot）是一种很有前途的siRNA表达质粒基因传递系统，与转染相关的异质性较小。(C) 2005 Elsevier B.V.版权所有
A multifunctional envelope-type nano device (MEND) for use in the delivery of siRNA expression plasmids is described. The plasmid DNA encoding anti-luciferase short interfering RNA (siRNA) was condensed by poly-L-lysine (PLL) and packaged into the MEND. The silencing effect of the MEND(PLL) showed a 96% inhibition of luciferase activities in a co-transfection study. The silencing effect was maintained at more than 60%, even under the 100-fold diluted conditions. In the luciferase transformed cells, however, the MEND(PLL) showed no significant silencing effect (10%), indicating heterogeneity in transfection by the MEND(PLL). To solve this problem, the DNA condensing agents were optimized by comparing PLL, stearyl octaarginine (STR-R8) and protamine (Prot). No difference in silencing effect (95-97%) was found among these MENDs in a co-transfection study. However, the MEND(Prot) showed a 70% silencing effect in the transformed cells. These results suggest that the MEND(Prot) has less heterogeneity in transfection, while the MEND(PLL) and the MEND(STR-R8) have large heterogeneities. These results demonstrate that MEND(Prot) is a promising gene delivery system for siRNA expression plasmids with less heterogeneity associated with the transfection. (C) 2005 Elsevier B.V. All rights reserved.