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Evidence for the role of proteoglycans in cation-mediated gene transfer

Mislick, Kimberly A. and Baldeschwieler, John D. (1996) Evidence for the role of proteoglycans in cation-mediated gene transfer. Proceedings of the National Academy of Sciences of the United States of America, 93 (22). pp. 12349-12354. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:MISpnas96

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Abstract

We report evidence that gene complexes, consisting of polycations and plasmid DNA enter cells via binding to membrane-associated proteoglycans. Treatment of HeLa cells with sodium chlorate, a potent inhibitor of proteoglycan sulfation, reduced luciferase expression by 69%. Cellular treatment with heparinase and chondroitinase ABC inhibited expression by 78% and 20% with respect to control cells. Transfection was dramatically inhibited by heparin and heparan sulfate and to a smaller extent by chondroitan sulfate B. Transfection of mutant, proteoglycan deficient Chinese hamster ovary cells was 53 x lower than of wild-type cells. For each of these assays, the intracellular uptake of DNA at 37 degrees C and the binding of DNA to the cell membrane at 4 degrees C was impaired. Preliminary transfection experiments conducted in mutant and wild-type Chinese hamster ovary cells suggest that transfection by some cationic lipids is also proteoglycan dependent. The variable distribution of proteoglycans among tissues may explain why some cell types are more susceptible to transfection than others.


Item Type:Article
Additional Information:Copyright © 1996 by the National Academy of Sciences. Contributed by John D. Baldeschwieler, August 9, 1996. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:HEPARAN-SULFATE PROTEOGLYCANS, CELLS, DNA, BIOSYNTHESIS, COMPLEXES, BIOLOGY
Record Number:CaltechAUTHORS:MISpnas96
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:MISpnas96
Alternative URL:http://www.pnas.org/cgi/content/abstract/93/22/12349
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1121
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Dec 2005
Last Modified:26 Dec 2012 08:42

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