Document Detail


The internalization route resulting in successful gene expression depends on both cell line and polyethylenimine polyplex type.
MedLine Citation:
PMID:  16979385     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Understanding cellular uptake and intracellular processing of nonviral gene delivery systems is a key aspect in developing more efficient vectors. In this study, the impact of clathrin- and caveolae/lipid-raft-dependent endocytosis on cell entry and overall transfection efficiency of polyethylenimine (PEI) polyplexes was evaluated. Most remarkably, the internalization pathway mediating successful transfection depended on both cell type and polyplex type applied. Colocalization studies with transferrin and cholera toxin B revealed that at least two specific endocytosis pathways--the clathrin-dependent and the lipid-raft-dependent--mediated cellular uptake of PEI polyplexes. With the help of specific uptake inhibitors (chlorpromazine and filipin III), cell-line-dependent variations regarding the route of successful transfection were observed (HUH-7, COS-7, HeLa). In COS-7 cells, the clathrin-dependent pathway was the main contributor to the transfection process. In HUH-7 cells, gene transfer by linear PEI polyplexes succeeded mainly via the clathrin-dependent route, whereas transfection by branched PEI polyplexes was mediated by both pathways. In HeLa cells, both pathways were able to mediate successful gene delivery. However, the lipid-raft-dependent pathway was more relevant. The study also revealed that the concentration window between specific inhibitory function and nonspecific toxicity of the uptake inhibitors was very narrow.
Authors:
Katharina von Gersdorff; Niek N Sanders; Roosmarijn Vandenbroucke; Stefaan C De Smedt; Ernst Wagner; Manfred Ogris
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-15
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  14     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-09     Completed Date:  2006-11-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  745-53     Citation Subset:  IM    
Affiliation:
Pharmaceutical Biology-Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, D-81377 Munich, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Survival
Cercopithecus aethiops
Endocytosis
Gene Expression*
Genes, Reporter / genetics
Humans
Polyethyleneimine*
Transfection / methods*
Transferrin / genetics,  metabolism
Chemical
Reg. No./Substance:
11096-37-0/Transferrin; 9002-98-6/Polyethyleneimine

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


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