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Synthesis of a novel series of cationic lipids that can act as efficient gene delivery vehicles through systematic heterocyclic substitution of cholesterol derivatives

Gene Therapy volume 8, pages 855–863 (2001)Cite this article

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.

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Acknowledgements

We thank Professor Leaf Huang for his comments on the manuscript. This research is supported by grants from the National Medical Research Council of Singapore and the Singapore National Science and Technology Board.

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

    H Gao & K M Hui

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  1. H Gao
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  2. K M Hui
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Gao, H., Hui, K. Synthesis of a novel series of cationic lipids that can act as efficient gene delivery vehicles through systematic heterocyclic substitution of cholesterol derivatives. Gene Ther 8, 855–863 (2001). https://doi.org/10.1038/sj.gt.3301471

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