Reducible poly(amido ethylenimine)-based gene delivery system for improved nucleus trafficking of plasmid DNA.
Reducible poly(amido ethylenimine)-based gene delivery system for improved nucleus trafficking of plasmid DNA.
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DOI：
10.1021/bc9003525
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发表时间：
2010-02-17
影响因子：
4.7
通讯作者：
Kim, Sung Wan
中科院分区：
文献类型：
--
作者：
Jeong, Ji Hoon;Kim, Sun Hwa;Christensen, Lane V.;Feijen, Jan;Kim, Sung Wan
在非病毒基因递送系统中，质粒DNA在细胞核中的定位是表达质粒DNA中编码的所需治疗性蛋白质的先决条件。在这项研究中，一个可还原的聚合物为基础的基因传递系统，以改善细胞内运输和核转位的质粒DNA。该系统由两个组分组成，即具有嗜核蛋白NFκB重复结合序列的质粒DNA和可还原聚合物。以胱胺双丙烯酰胺和三乙基四胺为原料，通过Michael型加成聚合反应合成了可还原的聚（TETA-CBA）。与质粒DNA形成紧密复合物的聚合物可在还原性胞质溶胶中降解以释放质粒DNA。胞浆中的触发释放机制可促进胞浆NFκB与具有重复NFκB结合基序的质粒DNA之间的相互作用。IL-1 β激活NFκB后，分布于细胞质中的质粒大部分定位于细胞核内，基因转染效率显著高于非降解PEI对照组。目前的研究表明，通过利用内源性转运机制进行质粒DNA的细胞内运输和核转位来提高转染效率的另一种方法。
In a non-viral gene delivery system, localization of a plasmid DNA in the nucleus is a prerequisite for expression of a desired therapeutic protein encoded in the plasmid DNA. In this study, a reducible polymer-based gene delivery system for improved intracellular trafficking and nuclear translocation of plasmid DNA is introduced. The system is consisted of two components, a plasmid DNA having repeated biding sequence for a karyophilic protein, NFκB, and a reducible polymer. A reducible poly(amido ethylenimine), poly(TETA-CBA), was synthesized by a Michael-type addition polymerization between cystamine bisacrylamide and triethyl tetramine. The polymer forming tight complexes with plasmid DNA could be degraded in the reductive cytosol to release the plasmid DNA. The triggered release mechanism in the cytosol could facilitate the interaction between cytosolic NFκB and the plasmid DNA having repeated NFκB biding motif. Upon activation of NFκB by interleukin-1β (IL-1β), the most of plasmid distributed in the cytoplasm was localized within the nucleus, resulting in significantly higher gene transfection efficiency than controls with non-degradable PEI. The current study suggests an alternative way of improving transfection efficiency by taking advantage of endogenous transport machinery for intracellular trafficking and nuclear translocation of a plasmid DNA.
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影响因子：
14.9
作者：
Read ML;Singh S;Ahmed Z;Stevenson M;Briggs SS;Oupicky D;Barrett LB;Spice R;Kendall M;Berry M;Preece JA;Logan A;Seymour LW
通讯作者：
Seymour LW
影响因子：
12.4
作者：
Mesika, A;Grigoreva, I;Reich, Z
通讯作者：
Reich, Z
DOI：
10.1073/pnas.92.10.4572
发表时间：
1995-05-09
影响因子：
11.1
作者：
DOWTY, ME;WILLIAMS, P;WOLFF, JA
通讯作者：
WOLFF, JA
影响因子：
12.4
作者：
Choi, S;Oh, S;Kim, SW
通讯作者：
Kim, SW
影响因子：
4.7
作者：
Christensen, Lane V.;Chang, Chien-Wen;Feijen, Jan
通讯作者：
Feijen, Jan