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A Stopped-Flow Kinetic Study of the Assembly of Nonviral Gene Delivery Complexes
dc.contributor.author | Braun, Chad S. | |
dc.contributor.author | Fisher, Mark T. | |
dc.contributor.author | Tomalia, Donald A. | |
dc.contributor.author | Koe, Gary S. | |
dc.contributor.author | Koe, Janet G. | |
dc.contributor.author | Middaugh, C. Russell | |
dc.date.accessioned | 2015-05-08T19:15:21Z | |
dc.date.available | 2015-05-08T19:15:21Z | |
dc.date.issued | 2005-06 | |
dc.identifier.citation | Braun et. al. "A Stopped-Flow Kinetic Study of the Assembly of Nonviral Gene Delivery Complexes." Volume 88, Issue 6, June 2005, Pages 4146–4158. http://dx.doi.org/10.1529/biophysj.104.055202 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17666 | |
dc.description.abstract | Stopped-flow circular dichroism and fluorescence spectroscopy are used to characterize the assembly of complexes consisting of plasmid DNA bound to the cationic lipids dimethyldioctadecylammonium bromide and 1, 2-dioleoyl- 3- trimethylammonium-propane and a series of polyamidoamine dendrimers. The kinetics of complexation determined from the stopped-flow circular dichroism measurements suggests complexation occurs within 50 ms. Further analysis, however, was precluded by the presence of mixing (shear) artifacts. Stopped-flow fluorescence employing the high-affinity DNA dyes Hoechst 33258 and YOYO-1 was able to resolve two sequential steps in the assembly of complexes that are assigned to binding/ dehydration and condensation events. The rates of each process were determined over the temperature range of 10–50 C and activation energies were determined from the slope of Arrhenius plots. The behavior of polyamidoamine dendrimers can be separated into two classes based on their differing binding modes: generation 2 and the larger generations (G4, G7, and G9). The larger generations have activation energies for binding that follow the trend G4 . G7 . G9. The activation energies for condensation (compaction) of complexes composed of these same dendrimers have the opposite trend G9 . G7 . G4. It is postulated that a balance between a more energetically favorable condensation and less favorable binding may prove beneficial in enhancing gene delivery. | en_US |
dc.publisher | Biophysical Society | en_US |
dc.title | A Stopped-Flow Kinetic Study of the Assembly of Nonviral Gene Delivery Complexes | en_US |
dc.type | Article | |
kusw.kuauthor | Braun, Chad S. | |
kusw.kuauthor | Fisher, Mark T. | |
kusw.kuauthor | Middaugh, C. Russell | |
kusw.kudepartment | Department of Pharmaceutical Chemisty | en_US |
dc.identifier.doi | 10.1529/biophysj.104.055202 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |