Mannose polyethylenimine conjugates for targeted DNA delivery into dendritic cells
Mannose polyethylenimine conjugates for targeted DNA delivery into dendritic cells
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DOI：
10.1074/jbc.274.27.19087
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发表时间：
1999-07-02
影响因子：
4.8
通讯作者：
Zenke, M
中科院分区：
文献类型：
--
作者：
Diebold, SS;Kursa, P;Zenke, M
细胞表面结合的受体代表通过受体介导的内吞作用将基因递送到细胞中的合适进入位点。在这里，我们已经利用甘露糖受体的抗原呈递树突状细胞上高度表达的靶向基因转移，通过采用甘露糖聚乙烯亚胺（ManPEI）共轭物。合成了几种ManPEI缀合物并用于形成ManPEI/DNA转染复合物。缀合物在甘露糖和聚乙烯亚胺（PEI）之间的接头和PEI部分的大小方面不同。我们证明ManPEI转染在将DNA递送到表达甘露糖受体的细胞中是有效的。ManPEI/DNA复合物的摄取是受体特异性的，因为DNA递送可以与甘露糖基化白蛋白竞争。另外，将腺病毒颗粒掺入转染复合物中有效地增强转基因表达。这对于原代免疫活性树突细胞特别重要。本文证明，用含有腺病毒颗粒的ManPEI/DNA复合物转染的树突状细胞以抗原特异性方式有效激活T细胞受体转基因小鼠的T细胞。
Cell surface-bound receptors represent suitable entry sites for gene delivery into cells by receptor-mediated endocytosis. Here we have taken advantage of the mannose receptor that is highly expressed on antigen-presenting dendritic cells for targeted gene transfer by employing mannosylpolyethylenimine (ManPEI) conjugates. Several ManPEI conjugates were synthesized and used for formation of ManPEI/DNA transfection complexes. Conjugates differed in the Linker between mannose and polyethylenimine (PEI) and in the size of the PEI moiety. We demonstrate that ManPEI transfection is effective in delivering DNA into mannose receptor-expressing cells. Uptake of ManPEI/DNA complexes is receptor-specific, since DNA delivery can be competed with mannosylated albumin, Additionally, incorporation of adenovirus particles into transfection complexes effectively enhances transgene expression. This is particularly important for primary immunocompetent dendritic cells. It is demonstrated here that dendritic cells transfected with ManPEI/DNA complexes containing adenovirus particles are effective in activating T cells of T cell receptor transgenic mice in an antigen-specific fashion.