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Polyion complex micelles as vectors in gene therapy – pharmacokinetics and in vivo gene transfer

Gene Therapy volume 9, pages 407–414 (2002)Cite this article

Abstract

To establish non-viral gene delivery systems for intravenous administration, complexes of DNA and block copolymer consisting of poly-L-lysine and poly(ethylene glycol) were tested in in vivo turnover studies. The polyion complex micelles have self-assembling core-shell structures, yielding spherical nano-particles with small absolute values of ζ-potential. Southern blot analysis showed that supercoiled DNA was observed for 30 min and open circular or linear DNA was seen for 3 h after intravenous administration of PIC micelles having the charge ratios of 1:4 and PLL length of 48 mer. The PIC micelles with shorter PLL length showed lower stability in the blood stream suggesting that DNA is able to persist as an intact molecule in the blood stream using this system. Though having no ligands, PIC micelles with charge ratios of 1:2 and 1:4 transfected efficiently into HepG2 cells. Preincubation with free copolymer inhibited expression of the reporter gene, suggesting that adsorption of block copolymer to the cell surface blocked the interaction site of the PIC micelles. When the PIC micelles were injected via supramesenteric vein, expression of the gene was observed only in the liver and was sustained for 3 days. It was suggested that this gene delivery system is intrinsically efficient.

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Acknowledgements

This work was supported by grants from Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research (OPSR) of Japan and a Grant-in-Aid for Scientific Research (11838022) and the Special Coordination Funds for Promoting Science and Technology, Ministry of Education, Science, Sports and Culture, Japan. We thank Dr Kaenji Kangown for helpful discussion, Dr Patrick Leahy for proofreading this article, Dr Hisayuki Matsuo for encouragement during this project, and Mrs Keiko Jinno for her excellent technical assistance.

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Authors and Affiliations

  1. National Cardiovascular Center Research Institute, Osaka, Japan

    M Harada-Shiba, I Takamisawa & K Shimokado

  2. Department of Materials Science, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

    K Yamauchi, A Harada & K Kataoka

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  1. M Harada-Shiba
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  2. K Yamauchi
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Harada-Shiba, M., Yamauchi, K., Harada, A. et al. Polyion complex micelles as vectors in gene therapy – pharmacokinetics and in vivo gene transfer. Gene Ther 9, 407–414 (2002). https://doi.org/10.1038/sj.gt.3301665

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