The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection
The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection
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DOI：
10.1016/j.biomaterials.2008.09.042
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发表时间：
2009-01-01
期刊：
影响因子：
14
通讯作者：
Nagasaki, Takeshi
中科院分区：
文献类型：
--
作者：
Kakimoto, Shinji;Hamada, Tsutomu;Nagasaki, Takeshi
众所周知，内体逃逸是非病毒基因传递的一个严重障碍。这是由于内溶体/溶酶体内容物的酸性和酶降解所致。因此，内化基因需要高效地释放到胞质中，才能获得高效的转染效率。另一方面，由于pH值的降低，白喉毒素T结构域与内体膜融合，从而促进白喉毒素C片段的内体逃逸。在本研究中，我们构建了白喉毒素T结构域共轭多亚胺（PEI）多聚体以促进外源基因的内体逃逸。白喉毒素T结构域与PEI/pDNA复合体结合后，与普通PEI/pDNA复合体相比，转染效率显著提高。白喉毒素T结构域疏水性的ph响应性增加不仅可能引起内吞囊泡膜的扰动，而且可能增加膜的通透性。(C) 2008 Elsevier Ltd版权所有。
The endosomal escape is a well-known serious obstacle for non-viral gene delivery. This is because of an acidic and enzymatic degradation of the contents of the endosome/lysosome. Therefore, the internalized gene needs to be efficient released into the cytosol to obtain the efficiently transfection efficiency. On the other hand, the diphtheria toxin T domain fuses with endosome membrane by pH decrease, then enhances the endosomal escape of the diphtheria toxin C fragment. In this study, we constructed diphtheria toxin T domain-conjugated poly(ethylenimine)s (PEI) polyplex for enhancing the endosomal escape of exogenous gene. The conjugation of diphtheria toxin T domain with PEI/pDNA polyplex leads to the significant enhancement of transfection efficiency when compared with plain PEI/pDNA polyplex. The pH-responsive increase in hydrophobicity of the diphtheria toxin T domain might not only trigger the perturbation of the endocytic vesicle membrane but might also increase the membrane permeability. (C) 2008 Elsevier Ltd. All rights reserved.