药学学报, 2014, 49(8): 1111-1116
王文喜, 代凯, 洪璐, 蔡婷, 唐岚. 基因胞内传递中的内体逃逸技术[J]. 药学学报, 2014, 49(8): 1111-1116.
WANG Wen-xi, DAI Kai, HONG Lu, CAI Ting, TANG Lan. The strategies of endosomal escape for intracellular gene delivery[J]. Acta Pharmaceutica Sinica, 2014, 49(8): 1111-1116.

王文喜, 代凯, 洪璐, 蔡婷, 唐岚
浙江工业大学药学院, 浙江 杭州 310032
基因在细胞内的传递过程及胞内分布对其作用至关重要,成功的基因载体应能有效地克服内体膜 的屏障将基因送到特定的细胞器。传统的非病毒类载体由于不能有效地绕过内体途径,故具有较低的转染活性,从而限制了基因药物的应用。为了进一步提高外源基因的转染效率,已发现大量的促进内体逃逸的试剂。这些试剂可通过与内体膜融合、在内体膜内形成小孔、光激活的破膜作用或质子海绵效应等机制促进内体逃逸。本文总结了文献报道的各种内体逃逸技术,根据其作用机制的不同对其分类阐述,并说明其在基因胞内传递中的应用。
关键词:    基因传递      内体逃逸      致孔      质子海绵效应      膜融合      光化学内化     
The strategies of endosomal escape for intracellular gene delivery
WANG Wen-xi, DAI Kai, HONG Lu, CAI Ting, TANG Lan
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China
The intracellular trafficking and subcellular distribution of exogenous gene is very important for gene delivery. A successful gene vehicle should overcome various barriers including endosomal membrane bar-riers to delivery gene to the target organelle. Traditional nonviral vehicle is unable to avoid endosomal pathway efficiently, so the efficiency of gene delivery is low and the application of gene drugs is limited. In order to achieve efficient nonviral gene delivery, a lot of researches based on endosomal escape have been carried out and some agents with the function of endsomal escape have been found. These agents facilitate the endsomal escape via various mechanisms, such as fusion into the lipid bilayer of endosomes, pore formation in the endosomal membrane, proton sponge effect and photochemical methods to rupture the endosomal membrane. In this review, various reported strategies for endsomal escape are described according to the escape mechanisms, and their applications in intracellular gene delivery are also discussed.
Key words:    gene delivery    endosomal escape    pore formation    proton sponge effect    membrane fusion    photochemical internalization   
收稿日期: 2014-01-03
基金项目: 国家自然科学基金资助项目(81102396)
通讯作者: 王文喜 Tel:86-571-88320722,Fax:86-571-88320320,E-mail:yjw@zjut.edu.cn
Email: yjw@zjut.edu.cn
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