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Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation

Gene Therapy volume 14, pages 1029–1038 (2007)Cite this article

Abstract

Gene therapy, a promising treatment for vascular disease, requires appropriate gene vectors with high gene transfer efficiency, good biocompatibility and low cytotoxicity. To satisfy these requirements from the approach of nonviral vectors, a novel block copolymer, poly(ethylene glycol) (PEG)-block-polycation, carrying ethylenediamine units in the side chain (PEG-b-P[Asp(DET)]) was prepared. PEG-b-P[Asp(DET)] formed a polyplex micelle through polyion complex formation with plasmid DNA (pDNA). The PEG-b-P[Asp(DET)] polyplex micelle showed efficient gene expression with low cytotoxicity against vascular smooth muscle cells in vitro. It also showed reduced interactions with blood components, offering its feasibility of gene delivery via the vessel lumen. To evaluate in vivo gene transfer efficiency for vascular lesions, PEG-b-P[Asp(DET)] micelle was instilled into rabbit carotid artery with neointima by an intravascular method, and expression of the reporter gene in vascular lesions was assessed. Polyplexes from homopolymer P[Asp(DET)] and branched polyethyleneimine (BPEI) were used as controls. Ultimately, only the polyplex micelle showed appreciable gene transfer into vascular lesions without any vessel occlusion by thrombus, which was in strong contrast to BPEI and P[Asp(DET)] polyplexes which frequently showed occlusion with thrombus. These findings suggest that the PEG-b-P[Asp(DET)] polyplex micelle may have promising potential as a nonviral vector for the treatment of vascular diseases.

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Acknowledgements

This work was supported by The Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and the Core Research Program for Evolutional Science and Technology (CREST) from the Japan Science and Technology Corporation (JST). We are especially grateful to Drs Yuichi Yamasaki, Keiji Itaka, Kensuke Osada, Kanjiro Miyata, Mr Satoru Matsumoto and Mr Shunsaku Asano (The University of Tokyo) for their special technical advice. We thank Dr Makoto Kaneko and Professor Yutaka Yatomi (The University of Tokyo) for supporting us at assessing platelet aggregation. And we also thank Mr Noboru Sunaga Ms Junko Kawakita for their assistance.

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Authors and Affiliations

  1. Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    D Akagi, T Miyata & H Nagawa

  2. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    D Akagi, S Fukushima & K Kataoka

  3. Department of Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    M Oba & H Koyama

  4. Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    N Nishiyama & K Kataoka

  5. Center for NanoBio Integration, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    K Kataoka

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  1. D Akagi
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Correspondence to K Kataoka.

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Akagi, D., Oba, M., Koyama, H. et al. Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation. Gene Ther 14, 1029–1038 (2007). https://doi.org/10.1038/sj.gt.3302945

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  • DOI: https://doi.org/10.1038/sj.gt.3302945

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