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June 2001, Volume 8, Number 11, Pages 855-863
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Research Article
Synthesis of a novel series of cationic lipids that can act as efficient gene delivery vehicles through systematic heterocyclic substitution of cholesterol derivatives
H Gao and K M Hui

Gene Vector Laboratory, Division of Cellular and Molecular Research, National Cancer Center, 11 Hospital Drive, Singapore 169610

Correspondence to: K M Hui

Abstract

The synthesis of a series of novel cationic lipids through the systematic substitution of cholesterol derivatives that could greatly enhance the delivery and expression of plasmid DNA in vitro and in vivo is described. Two of the newly synthesized lipids, designated as NCC4 and NCC10, were chosen to be studied in detail and gave much higher levels of gene expression than that which could be obtained with some of the conventional cationic polymers and cationic liposomes. In vivo studies with both NCC4 and NCC10 also showed better ability in delivering the reporter gene to the target cells through intrasplenic injection. In addition, by varying the DNA/lipid charge ratios, NCC4 and NCC10 can withstand serum inactivation in vitro. However, this does not correlate with the corresponding increase in the level of gene expression following systemic gene delivery with NCC4 and NCC10 in vivo. Gene Therapy (2001) 8, 855-863.

Keywords

cationic liposomes; cancer gene therapy; gene delivery; heterocyclic cholesterol; serum inactivation

Received 30 October 2000; accepted 9 March 2001
June 2001, Volume 8, Number 11, Pages 855-863
Table of contents    Previous  Abstract  Next   Full text  PDF
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