Enhanced gene delivery using disulfide-crosslinked low molecular weight polyethylenimine with listeriolysin o-polyethylenimine disulfide conjugate.
Enhanced gene delivery using disulfide-crosslinked low molecular weight polyethylenimine with listeriolysin o-polyethylenimine disulfide conjugate.
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DOI：
10.1016/j.jconrel.2008.07.007
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发表时间：
2008-10-06
影响因子：
10.8
通讯作者：
Lee, Kyung-Dall
中科院分区：
文献类型：
--
作者：
Choi, Suna;Lee, Kyung-Dall
对非病毒基因递送系统的最重要要求之一是以低毒性介导高水平基因表达的能力。在DNA/载体复合物通过内吞作用被细胞摄取后，DNA通常包含在内吞区室中，并且由于内体和溶酶体内的低pH和水解酶而快速降解，限制了其进入胞质溶胶并最终进入细胞核。在这项研究中，来自细胞内病原体单核细胞增生李斯特菌的胞内体溶解蛋白溶血素O（LLO）通过可逆二硫键与平均分子量为25 kDa（PEI 25）的聚乙烯亚胺（PEI）缀合（LLO-s-s-PEI），并掺入与二硫键交联的低分子量PEI 1.8 kDa（PEI 1.8）缩合的质粒DNA中。我们已经研究并证明，高基因转染效率，这是由最常用的PEI 25相比，可以通过可逆交联低分子量PEI（PEI 1.8）使用二硫键，大大降低了PEI的细胞毒性。通过使用合成的LLO-s-s-PEI缀合物，将LLO可逆地掺入PEI的DNA缩合物中，进一步增强了转染效率，超过了单独使用二硫键交联的PEI 1.8的DNA缩合物的转染效率。
One of the most important requirements for non-viral gene delivery systems is the ability to mediate high levels of gene expression with low toxicity. After the DNA/vector complexes are taken up by cells through endocytosis, DNA is typically contained within the endocytic compartments and rapidly degraded due to the low pH and hydrolytic enzymes within endosomes and lysosomes, limiting its accessibility to the cytosol and ultimately to the nucleus. In this study, the endosomolytic protein listeriolysin O (LLO) from the intracellular pathogen Listeria monocytogenes was conjugated with polyethylenimine (PEI) of average molecular weight 25 kDa (PEI25) via a reversible disulfide bond (LLO-s-s-PEI), and incorporated into plasmid DNA condensed with disulfide-crosslinked low molecular weight PEI 1.8 kDa (PEI1.8). We have investigated and demonstrated that high gene transfection efficiency, which is comparable to that by the most commonly used PEI25, can be achieved by reversibly crosslinking low molecular weight PEI (PEI1.8) using disulfide bonds, with greatly reduced cytotoxicity of the PEI. The reversible incorporation of LLO into the DNA condensates of PEI, through the use of the synthesized LLO-s-s-PEI conjugate, further enhances the transfection efficiency beyond that of DNA condensates with disulfide-crosslinked PEI1.8 alone.
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影响因子：
10.8
作者：
von Harpe, A;Petersen, H;Kissel, T
通讯作者：
Kissel, T
影响因子：
10.8
作者：
Ahn, CH;Chae, SY;Kim, SW
通讯作者：
Kim, SW
影响因子：
4.7
作者：
Gosselin, MA;Guo, WJ;Lee, RJ
通讯作者：
Lee, RJ
影响因子：
5.1
作者：
Saito, G;Amidon, GL;Lee, KD
通讯作者：
Lee, KD
DOI：
10.1111/j.1749-6632.1994.tb44235.x
发表时间：
1994-01-01
期刊：
MICROBIAL PATHOGENESIS AND IMMUNE RESPONSE
影响因子：
--
作者：
PORTNOY, DA;JONES, S
通讯作者：
JONES, S