A versatile linker for nontoxic polyamine-mediated DNA transfection

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Low levels of transfection efficacy and lipid-associated cytotoxicity have complicated the use of cationic lipids to facilitate transfer of exogenous DNA to eukaryotic cells. To address these issues, we synthesized a panel of six tetraester polyamines that were designed to minimize cytotoxicity by using pentaerythritol to link the hydrophobic and the DNA-binding domains. We conducted this study to probe the effects of structural modifications around pentaerythritol as a linker on transfection activity and cell viability. We compared polyamines against commercial lipid reagents using luciferase and green fluorescent protein transfection assays in both CHO and NIH3T3 cells. Measurement of transfection activity and cytotoxicity using flow cytometry showed that the more active polyamine analogs exhibited activities comparable to LipofectAMINE PLUS and TransFast. Flow cytometry analyses revealed that all the pentaerythritol-based polyamines were uniformly nontoxic, whereas transfection activity was dependent on headgroup and sidechain composition. These results demonstrate that pentaerythritol is a useful core material for the development of active, nontoxic transfection agents.




Niedzinski, E. J., Fujii, S. K., Lizarzaburu, M. E., Hecker, J. G., & Nantz, M. H. (2002). A versatile linker for nontoxic polyamine-mediated DNA transfection. Molecular Therapy, 6(2), 279–286. https://doi.org/10.1006/mthe.2002.0645

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