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Published November 28, 2006 | public
Journal Article

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

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.

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.

Additional details

Created:
August 22, 2023
Modified:
October 23, 2023