Structure/property studies of polymeric gene delivery using a library of poly(β-amino esters)

被引:292
作者
Anderson, DG [1 ]
Akinc, A [1 ]
Hossain, N [1 ]
Langer, R [1 ]
机构
[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
关键词
D O I
10.1016/j.ymthe.2004.11.015
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Here we describe the synthesis and characterization of a library of 486 second-generation poly(beta-amino esters). To understand better the structure/property relationships governing polymeric gene delivery, we synthesized polymers with 70 different primary structures, at 6 to 12 different molecular weights, using monomers previously identified as common to effective gene delivery polymers. This library was characterized by (1) molecular weight, (2) particle size upon complexation with DNA, (3) surface charge upon complexation with DNA, (4) optimal polymer/ DNA ratio, and (5) transfection efficiency. in this library, polymers with 20 of the 70 primary structures possess transfection efficiencies as good as or better than one of the best commercially available lipid reagents, Lipofectamine 2000. In general, the most effective polymers condense DNA into sub-150-nm complexes with positive surface charge. Among this group, the 2 most effective polymers condensed DNA to the smallest particle sizes (71 and 79 nm). Interestingly, the top 9 polymers were all formed from amino alcohols, and the structure of the 3 top performing polymers differs by only one carbon. This convergence in structure of the top performing polymers suggests a common mode of action and provides a framework with which future polymers can be designed.
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收藏
页码:426 / 434
页数:9
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