阳离子超支化缩水甘油醚衍生物对提高腺病毒载体基因表达率的体外研究
Enhanced in vitro gene expression efficacy of the adenovirus mediated by cationic hyperbranched polyglycerol derivatives
作者：汪婷;张志荣;龚涛;孙逊;
Author：
收稿日期： 年卷（期）页码：2017,32(05):-514-517
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：阳离子化;超支化缩水甘油醚衍生物;重组腺病毒;基因表达,静电复合;细胞摄取;细胞转导;基因传递
Key words：
基金项目：
中文摘要
目的制备阳离子超支化缩水甘油醚衍生物HPG-AGE-cys(HPAC),将其包裹在腺病毒(r Ad)表面形成复合物,探究其提高腺病毒基因表达效率的能力。方法采用阴离子开环聚合反应制备超支化缩水甘油醚,并进一步阳离子衍生化得到HPAC,其结构经核磁确证;通过静电复合作用制备材料-腺病毒复合物,并测定其粒径和Zeta电位,用透射电镜观察其表面形态;考察了复合物被A549细胞、CHO细胞和MDCK细胞摄取的能力和细胞转导的能力。结果成功合成了阳离子超支化缩水甘油醚衍生物HPAC,制备了HPAC-r Ad复合物。其平均粒径为128.8±3.8 nm,Zeta电位为29.8±5.2 m V;与裸病毒r Ad比较,复合物被细胞摄取的能力和细胞转导的能力均有显著提高。结论阳离子超支化缩水甘油醚衍生物材料合成方法简单易行,制备的HPAC-r Ad复合物能够显著提高病毒的基因效率,在腺病毒的基因传递方面具有广阔的应用前景。
参考文献
[1]Noureddini SC,Curiel DT.Genetic targeting strategies for adenovirus[J].Mol Pharmaceut,2005,2(5):341-347.
[2]Kang Q,Sun MH,Cheng H,et al.Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery[J].Gene Ther,2004,11(17):1312-1320.
[3]Sharma P,Kolawole AO,Wiltshire SM,et al.Accessibility of the coxsackievirus and adenovirus receptor and its importance in adenovirus gene transduction efficiency[J].J Gen Virolo,2012,93(1):155-158.
[4]Schneider H,Groves M,Mühle C,et al.Retargeting of adenoviral vectors to neurons using the H C fragment of tetanus toxin[J].Gene Ther,2000,7.
[5]Yotnda P,Chen DH,Chiu W,et al.Bilamellar cationic liposomes protect adenovectors from preexisting humoral immune responses[J].Mol Ther,2002,5:233-241.
[6]Wortmann A,V9hringer S,Engler T,et al.Fully detargeted polyethylene glycol-coated adenovirus vectors are potent genetic vaccines and escape from pre-existing anti-adenovirus antibodies[J].Mol Ther,2008,16:154-162.
[7]Kainthan RK,Janzen J,Levin E,et al.Biocompatibility testing of branched and linear polyglycidol[J].Biomacromolecules,2006,7(3):703-709.
[8]Dodds E,Piper TA,Murphy SJ,et al.Cationic lipids and polymers are able to enhance adenoviral infection of cultured mouse myotubes[J].J Neurochem,1999,72(5):2105-2112.
【关闭】
