Mishra, Swaroop and Heidel, Jeremy D. and Webster, Paul and Davis, Mark E. (2006) Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes. Journal of Controlled Release, 116 (2). pp. 179-191. ISSN 0168-3659. doi:10.1016/j.jconrel.2006.06.018. https://resolver.caltech.edu/CaltechAUTHORS:20110714-113854842
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Abstract
The linear, cyclodextrin-containing polycation (CDP) is one of many non-viral gene delivery vectors that show improved transfection efficiency when modified to have pH-buffering capacity. The buffering activity is presumed to confer enhanced ability to escape the endocytic pathway. Here, the differences in delivery behavior between CDP and its pH-buffering, imidazole-containing variant (CDPim) are investigated in order to elucidate the mechanism(s) by which these related materials exhibit differences in gene delivery. In cell-free assays that include dye exclusion and heparan sulfate displacement, CDP appears to have weaker binding strength with nucleic acids than CDPim. Numerous analyses involving transfected cells, however, indicate that CDPim more readily releases nucleic acids in the intracellular setting. Together, these data suggest that differences in transfection efficiency between CDP and CDPim result from factors beyond buffering activity and endosomal escape.
Item Type: | Article | |||||||||
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Additional Information: | © 2006 Elsevier. Received 1 April 2006; accepted 21 June 2006. Available online 27 June 2006. We are grateful to Patrick Midoux for his kind gift of the 293-T7 cells and the plasmid pT7Luc, and we thank Insert Therapeutics, Inc. for partial support of this work. | |||||||||
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Subject Keywords: | polyplexes; gene delivery; buffering; endosomal escape; cyclodextrin polymer | |||||||||
Issue or Number: | 2 | |||||||||
DOI: | 10.1016/j.jconrel.2006.06.018 | |||||||||
Record Number: | CaltechAUTHORS:20110714-113854842 | |||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20110714-113854842 | |||||||||
Official Citation: | Swaroop Mishra, Jeremy D. Heidel, Paul Webster, Mark E. Davis, Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes, Journal of Controlled Release, Volume 116, Issue 2, Proceedings of the Ninth European Symposium on Controlled Drug Delivery, 28 November 2006, Pages 179-191, ISSN 0168-3659, DOI: 10.1016/j.jconrel.2006.06.018. (http://www.sciencedirect.com/science/article/pii/S016836590600321X) | |||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
ID Code: | 24422 | |||||||||
Collection: | CaltechAUTHORS | |||||||||
Deposited By: | Tony Diaz | |||||||||
Deposited On: | 04 Oct 2011 21:10 | |||||||||
Last Modified: | 09 Nov 2021 16:23 |
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