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A novel gemini-like cationic lipid for the efficient delivery of siRNA
Zheng, Yi; Guo, Yujia; Li, Yating; Wu, Yun; Zhang, Lihe; Yang, Zhenjun
刊名NEW JOURNAL OF CHEMISTRY
2014-10-01
DOI10.1039/c4nj00531g
38期:10页:4952-4962
收录类别SCI ; IC
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary
资助者Ministry of Science and Technology of China (the National Key Basic Research Program of China) ; National Natural Science Foundation of China ; Ministry of Science and Technology of China (the National Key Basic Research Program of China) ; National Natural Science Foundation of China
研究领域[WOS]Chemistry
关键词[WOS]CLINICAL-TRIALS WORLDWIDE ; GENE DELIVERY ; ANTISENSE OLIGONUCLEOTIDES ; TRANSFECTION PROPERTIES ; RNA INTERFERENCE ; MAMMALIAN-CELLS ; IN-VITRO ; NANOPARTICLES ; THERAPY ; DNA
英文摘要

Although RNAi is a promising strategy for the intervention of human diseases, an essential prerequisite is the development of low-toxic and efficient siRNA delivery systems. In this report, we describe a novel gemini-like cationic lipid (CLD) that was developed and evaluated for the delivery of siRNA. The novel lipid contains a disulfide bond in the spacer, which can be cleaved under reductive conditions in the cytoplasm and decrease lipid toxicity. The liposomes formed by CLD exhibited a high siRNA binding property, which was facilitated by the increased number of cationic charges. Moreover, the cationic lipids showed tow cytotoxicity. They protected siRNAs from degradation by nucleases and the complexed siRNA was released efficiently in the presence of low concentrations of polyanionic heparin. High content screening and confocal microscopy studies demonstrated that lipoplexes with FAM labeled siRNA showed efficient cell uptake by HeLa and A375 cells. Finally, siRNA targeting MEK1 mRNA formulated in Liposomes demonstrated effective endosomal escape after cellular uptake and efficient gene silencing of MEK1 expression. These results demonstrated the promising use of the novel gemini-like cationic lipid for the efficient and safe delivery of siRNA.

语种英语
所属项目编号2012CB720604 ; 2012AA022501 ; 20932001
资助者Ministry of Science and Technology of China (the National Key Basic Research Program of China) ; National Natural Science Foundation of China ; Ministry of Science and Technology of China (the National Key Basic Research Program of China) ; National Natural Science Foundation of China
WOS记录号WOS:000342725800042
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66756
专题北京大学药学院
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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GB/T 7714
Zheng, Yi,Guo, Yujia,Li, Yating,et al. A novel gemini-like cationic lipid for the efficient delivery of siRNA[J]. NEW JOURNAL OF CHEMISTRY,2014,38(10):4952-4962.
APA Zheng, Yi,Guo, Yujia,Li, Yating,Wu, Yun,Zhang, Lihe,&Yang, Zhenjun.(2014).A novel gemini-like cationic lipid for the efficient delivery of siRNA.NEW JOURNAL OF CHEMISTRY,38(10),4952-4962.
MLA Zheng, Yi,et al."A novel gemini-like cationic lipid for the efficient delivery of siRNA".NEW JOURNAL OF CHEMISTRY 38.10(2014):4952-4962.
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