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Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes

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. 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
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jconrel.2006.06.018DOIUNSPECIFIED
http://www.sciencedirect.com/science/article/pii/S016836590600321XPublisherUNSPECIFIED
ORCID:
AuthorORCID
Mishra, Swaroop0000-0002-2665-5385
Davis, Mark E.0000-0001-8294-1477
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.
Funders:
Funding AgencyGrant Number
Insert Therapeutics, Inc.UNSPECIFIED
Subject Keywords:polyplexes; gene delivery; buffering; endosomal escape; cyclodextrin polymer
Issue or Number:2
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 Mar 2020 13:19

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