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Dextran–spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection

Gene Therapy volume 11, pages 194–203 (2004)Cite this article

Abstract

Dextran–spermine cationic polysaccharide was prepared by means of reductive amination between oxidized dextran and the natural oligoamine spermine. The formed Schiff-base imine-based conjugate was reduced with borohydride to obtain the stable amine-based conjugate. The transfection efficiency of the synthetic dextran–spermine was assessed in vitro on HEK293 and NIH3T3 cell lines and found to be as high as the DOTAP/Chol 1/1 lipid-based transfection reagent. Modification of the dextran–spermine polycation with polyethylene glycol resulted in high transfection yield in serum-rich medium. Intramuscular injection in mice of dextran–spermine–pSV-LacZ complex induced high local gene expression compared to low expression of the naked DNA. Intravenous injection of a dispersion of the dextran–spermine–pSV-LacZ complex resulted with no expression in all examined organs. When the partially PEGylated dextran–spermine–pSV-LacZ complex was intravenously applied, a high gene expression was detected mainly in the liver. Preliminary targeting studies indicated that the PEGylated dextran–spermine–pSV-LacZ complex bound to galactose receptor of liver parenchymal cells rather than the mannose receptor of liver nonparenchymal cells. This work offers a new biodegradable polycation based on natural components, which is capable of transfecting cells and tissues in vitro and in vivo.

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Acknowledgements

Tony Azzam is grateful to the Ministry of Science, Israel, for its generous financial assistance. This work was supported in part by the AFIRST, French–Israeli Cooperation on Gene Therapy, and by the US–Israel Binational Fund (BSF).

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Author notes

  1. H Hosseinkhani and T Azzam: Equal contributors

  2. AJ Domb: AJD is affiliated with the David R Bloom Center for Pharmacy and with the Alex Grass Center for Drug Design and Synthesis at the Hebrew University of Jerusalem

Authors and Affiliations

  1. Department of Biomaterials, Field of Tissue Engineering, Kyoto University, Kyoto, Japan

    H Hosseinkhani & Y Tabata

  2. Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

    T Azzam & AJ Domb

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  1. H Hosseinkhani
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  2. T Azzam
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Hosseinkhani, H., Azzam, T., Tabata, Y. et al. Dextran–spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection. Gene Ther 11, 194–203 (2004). https://doi.org/10.1038/sj.gt.3302159

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