Mannose receptor-mediated gene delivery into antigen presenting dendritic cells.
Mannose receptor-mediated gene delivery into antigen presenting dendritic cells.
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DOI：
10.1023/a:1022975705406
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发表时间：
2002-11-01
期刊：
影响因子：
--
通讯作者：
Zenke, Martin
中科院分区：
文献类型：
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作者：
Diebold, Sandra S.;Plank, Christian;Zenke, Martin
树突状细胞是专职的抗原呈递细胞，并且在其引发初始T细胞的能力方面是独特的。树突状细胞的基因修饰对于免疫系统已经失败或异常调节的疾病的免疫治疗特别感兴趣，例如分别在癌症或自身免疫性疾病中。树突状细胞大量表达甘露糖受体和甘露糖受体相关受体，并且通过甘露糖受体的受体介导的基因转移为靶向基因递送到这些细胞中提供了通用工具。因此，产生甘露糖聚乙烯亚胺DNA转移复合物并用于将基因递送到树突细胞中。甘露糖受体属于清道夫受体组，其允许树突状细胞摄取致病物质，其被定向用于降解和MHC II类呈递。因此，通过甘露糖受体介导的基因递送的转基因表达的限制步骤是DNA的内体降解。已经探索了几种策略来克服这种限制，包括向DNA转移复合物如腺病毒颗粒和流感肽中加入内体溶解组分。在这里，我们回顾了目前的理解甘露糖受体介导的基因传递到树突状细胞，并讨论了策略，以确定适当的内体溶解剂，以提高DNA转移效率。
Dendritic cells are professional antigen presenting cells and are unique in their ability to prime naive T cells. Gene modification of dendritic cells is of particular interest for immunotherapy of diseases where the immune system has failed or is aberrantly regulated, such as in cancer or autoimmune disease, respectively. Dendritic cells abundantly express mannose receptor and mannose receptor-related receptors, and receptor-mediated gene transfer via mannose receptor offers a versatile tool for targeted gene delivery into these cells. Accordingly, mannose polyethylenimine DNA transfer complexes were generated and used for gene delivery into dendritic cells. Mannose receptor belongs to the group of scavenger receptors that allow dendritic cells to take up pathogenic material, which is directed for degradation and MHC class II presentation. Therefore, a limiting step of transgene expression by mannose receptor-mediated gene delivery is endosomal degradation of DNA. Several strategies have been explored to overcome this limitation including the addition of endosomolytic components to DNA transfer complexes like adenovirus particles and influenza peptides. Here, we review the current understanding of mannose receptor-mediated gene delivery into dendritic cells and discuss strategies to identify appropriate endosomolytic agents to improve DNA transfer efficacy.