Cellular uptake and activation characteristics of naked plasmid DNA and its cationic liposome complex in human macrophages.
Cellular uptake and activation characteristics of naked plasmid DNA and its cationic liposome complex in human macrophages.
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DOI：
10.1016/j.ijpharm.2005.08.020
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发表时间：
2005-11
影响因子：
5.8
通讯作者：
Ikuko Yamane;M. Nishikawa;Y. Takakura
中科院分区：
文献类型：
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作者：
Ikuko Yamane;M. Nishikawa;Y. Takakura
质粒DNA（pDNA）是一种重要的大分子治疗剂，适用于基于DNA的治疗，如非病毒基因治疗和DNA疫苗接种。已知在细菌DNA中丰富但在脊椎动物DNA中不丰富的未甲基化CpG基序触发炎症反应，其抑制转基因表达，同时调节疫苗接种后的免疫后果。我们研究了裸pDNA及其阳离子脂质体复合物在人巨噬细胞样细胞中的细胞摄取和活化特性。目前的研究表明，裸pDNA通过聚阴离子的特定机制被人巨噬细胞样细胞识别。此外，研究表明，pDNA与阳离子脂质体复合物以不依赖于CpG基序的方式激活人巨噬细胞样细胞诱导肿瘤坏死因子-α（TNF-α）的产生，而任何类型的裸DNA都不能诱导这些细胞产生TNF-α，无论pDNA或寡核苷酸（ODN）中是否存在CpG基序。这些发现为基于DNA的治疗（包括基因治疗和DNA疫苗接种）奠定了重要基础。
Plasmid DNA (pDNA) is an important macromolecular therapeutic agent suitable for DNA-based therapies, such as non-viral gene therapy and DNA vaccination. Unmethylated CpG motifs abundant in bacterial DNA, but not in vertebrate DNA, are known to trigger an inflammatory response, which inhibits transgene expression, while modulating immunological consequences following vaccination. We studied cellular uptake and activation characteristics of naked pDNA and its cationic liposome complex in human macrophage-like cells. The present study has demonstrated that naked pDNA was recognized by human macrophage-like cells via specific mechanisms for polyanions. Moreover, it has shown that pDNA complexed with cationic liposomes activates human macrophage-like cells to induce the production of tumor necrosis factor-α (TNF-α) in a CpG motif-independent manner, while any types of naked DNA could not induce TNF-α production from these cells, regardless of the presence of CpG motifs in pDNA or oligonucleotide (ODN). These findings form an important basis for DNA-based therapies including gene therapy and DNA vaccination.