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Mol Ther. 2005 Mar;11(3):426-34.

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

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Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.


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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