Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells

被引:427
作者
Thomas, M
Klibanov, AM [1 ]
机构
[1] MIT, Dept Chem, Cambridge, MA 02139 USA
[2] MIT, Div Biol Engn, Cambridge, MA 02139 USA
关键词
D O I
10.1073/pnas.192581499
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The effect of various chemical modifications of nitrogen atoms on the efficiency of polyethylenimines (PEIs) as synthetic vectors for the delivery of plasmid DNA into monkey kidney cells in vitro has been systematically investigated. The resultant structure-activity relationship has both provided mechanistic insights and led to PEI derivatives with markedly enhanced performance. For example, N-acylation of PEI with the molecular mass of 25 kDa (PE125, one of the most potent polycationic gene delivery vectors) with alanine nearly doubles its transfection efficiency in the presence of serum and also lowers its toxicity. Furthermore, dodecylation of primary amino groups of 2-kDa PEI yields a nontoxic polycation whose transfection efficiency in the presence of serum is 400 times higher than the parent's and which exceeds 5-fold even that of PE125.
引用
收藏
页码:14640 / 14645
页数:6
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