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  • Nonviral Transfer Technology
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Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes

Gene Therapy volume 7, pages 292–299 (2000)Cite this article

Abstract

A novel mannosylated cholesterol derivative, cholesten-5-yloxy-N-(4-((1-imino-2-β-D-thiomannosyl-ethyl)amino)butyl) formamide (Man-C4-Chol), was synthesized in order to perform mannose receptor-mediated gene transfer with liposomes. Plasmid DNA encoding luciferase gene (pCMV-Luc) complexed with liposomes, consisting of a 6:4 mixture of Man-C4-Chol and dioleoylphosphatidylethanolamine (DOPE), showed higher transfection activity than that complexed with 3β[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol)/DOPE(6:4) and N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/DOPE(1:1) liposomes in mouse peritoneal macrophages. The presence of 20 mM mannose significantly inhibited the transfection efficiency of pCMV-Luc complexed with Man-C4-Chol/DC- Chol/DOPE(3:3:4) and Man-C4-Chol/DOPE(6:4) liposomes. High gene expression of pCMV-Luc was observed in the liver after intravenously injecting mice with Man-C4-Chol/DOPE(6:4) liposomes, whereas DC-Chol/DOPE(6:4) liposomes only showed marked expression in the lung. The gene expression with Man-C4-Chol/DOPE(6:4) liposome/ DNA complexes in the liver was observed preferentially in the non-parenchymal cells and was significantly reduced by predosing with mannosylated bovine serum albumin. The gene expression in the liver was greater following intraportal injection. These results suggest that plasmid DNA complexed with mannosylated liposomes exhibits high transfection activity due to recognition by mannose receptors both in vitro and in vivo.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.

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Authors and Affiliations

  1. Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    S Kawakami, A Sato, M Nishikawa, F Yamashita & M Hashida

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  1. S Kawakami
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  2. A Sato
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  3. M Nishikawa
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  4. F Yamashita
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Kawakami, S., Sato, A., Nishikawa, M. et al. Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes. Gene Ther 7, 292–299 (2000). https://doi.org/10.1038/sj.gt.3301089

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