Document Detail


Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes.
MedLine Citation:
PMID:  16891028     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Swaroop Mishra; Jeremy D Heidel; Paul Webster; Mark E Davis
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-27
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  116     ISSN:  0168-3659     ISO Abbreviation:  J Control Release     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-12-12     Completed Date:  2007-02-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  179-91     Citation Subset:  IM    
Affiliation:
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
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MeSH Terms
Descriptor/Qualifier:
Buffers
Chloroquine / chemistry
Comet Assay / methods
DNA / chemistry,  genetics,  metabolism*
DNA Damage
Flow Cytometry
Hela Cells
Heparitin Sulfate / chemistry
Humans
Hydrogen-Ion Concentration
Imidazoles / chemistry*
Intercalating Agents / chemistry
Microscopy, Electron, Transmission
Nucleic Acid Conformation
Transfection / methods*
Transport Vesicles / metabolism,  ultrastructure
beta-Cyclodextrins / chemistry*
Chemical
Reg. No./Substance:
0/Buffers; 0/Imidazoles; 0/Intercalating Agents; 0/beta-Cyclodextrins; 54-05-7/Chloroquine; 9007-49-2/DNA; 9050-30-0/Heparitin Sulfate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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