Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (333K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (49)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Manunta, M.
Right arrow Articles by George, A. J. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Manunta, M.
Right arrow Articles by George, A. J. T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 17 May 2004

Nucleic Acids Research, 2004, Vol. 32, No. 9 2730-2739

Gene delivery by dendrimers operates via a cholesterol dependent pathway

Maria Manunta, Peng Hong Tan, Pervinder Sagoo, Kirk Kashefi1 and Andrew J. T. George*

Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK and 1 Department of Virology, Jefferiss Research Trust Laboratories, Wright Fleming Institute, Faculty of Medicine, Imperial College London, St Mary’s Hospital, Norfolk Place, London W2 1PG, UK

*To whom correspondence should be addressed. Tel: +44 20 8383 1475; Fax: +44 20 8383 2788; Email: a.george{at}imperial.ac.uk

Received March 10, 2004; Revised and Accepted April 19, 2004

Understanding the cellular uptake and intracellular trafficking of dendrimer–DNA complexes is an important prerequisite for improving the transfection efficiency of non-viral vector-mediated gene delivery. Dendrimers are synthetic polymers used for gene transfer. Although these cationic molecules show promise as versatile DNA carriers, very little is known about the mechanism of gene delivery. This paper investigates how the uptake occurs, using an endothelial cell line as model, and evaluates whether the internalization of dendriplexes takes place randomly on the cell surface or at preferential sites such as membrane rafts. Following extraction of plasma membrane cholesterol, the transfection efficiency of the gene delivered by dendrimers was drastically decreased. Replenishment of membrane cholesterol restored the gene expression. The binding and especially internalization of dendriplexes was strongly reduced by cholesterol depletion before transfection. However, cholesterol removal after transfection did not inhibit expression of the delivered gene. Fluorescent dendriplexes co-localize with the ganglioside GM1 present into membrane rafts in both an immunoprecipitation assay and confocal microscopy studies. These data strongly suggest that membrane cholesterol and raft integrity are physiologically relevant for the cellular uptake of dendrimer–DNA complexes. Hence these findings provide evidence that membrane rafts are important for the internalization of non-viral vectors in gene therapy.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
P. H. Tan, S.-A. Xue, M. Manunta, S. C. Beutelspacher, H. Fazekasova, A.K.M. Shamsul Alam, M. O. McClure, and A. J.T. George
Effect of Vectors on Human Endothelial Cell Signal Transduction: Implications for Cardiovascular Gene Therapy
Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 462 - 467.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.