カチオン性リポソームを用いた遺伝子医薬品の in vivo デリバリー
カチオン性リポソームを用いた遺伝子医薬品の in vivo デリバリー
复制标题
使用阳离子脂质体体内递送基因药物
DOI：
10.2745/dds.15.89
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发表时间：
2000
影响因子：
--
通讯作者：
中村 純三
中科院分区：
文献类型：
--
作者：
川上 茂;橋田 充;西田 孝洋;中村 純三
阳离子脂质体是一种潜在的非病毒基因载体，具有较低的免疫原性。阳离子脂质体的基因转移效率低于病毒载体，但近年来的研究表明，阳离子脂质体可以提高基因表达水平。阳离子脂质体的最大问题似乎是缺乏器官或细胞选择性，因为肺在静脉注射后显示最高的基因表达器官。将细胞特异性靶向技术应用于脂质体将改善体内基因递送并减少意外的副作用。肝实质细胞和肝非实质细胞分别专门表达大量高亲和力脱唾液酸糖蛋白和甘露糖受体。受体介导的基因传递系统似乎将外源DNA引入体内特定的细胞类型。然而，我们已经证实，不仅是性质的配体接枝到载体，而且整体的物理化学性质的复合物需要优化的细胞选择性靶向质粒DNA。本文从质粒DNA、质粒DNA/阳离子脂质体和糖基化阳离子脂质体的理化性质出发，对基因传递系统进行了评价。
Cationic liposomes have been considered as a potential non-viral vector for gene delivery, which possess a low immunogenicity unlike viral vectors. The gene transfer effcieney of cationic liposomes is lower than that of viral vectors but the advance of recent study revealed to enhance the gene expression levels of cationic liposomes. The most problem of cationic liposomes seem to be the lack of organ or cell selectivity because the lung shows highest gene expression organ after intravenous injection. Applying a cell-specific targeting technology to the liposomes would improve in vivo gene delivery and reduce unexpected side effects. Liver parencymal cells and liver non-parenchymal cells exclusively express large numbers of high affinity asialoglycoprotein and mannose receptors, respectively. Receptor-mediated gene delivery systems seems to introduce foreign DNA into specific cell types in vivo. However, we have confirmed that not only the nature of the ligands grafted to carriers but also the overall physicochemical properties of the complexes need to be optimized for the cell-selective targeting of plasmid DNA. In this article, we attempt to evaluate the the gene delivery system based on the physicochemical properties of plasmid DNA and plasmid DNA/cationic liposomes or glycosylated cationic liposomes.