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New delivery system for plasmid DNA in vivo using atelocollagen as a carrier material: the Minipellet

Nature Medicine volume 5, pages 707–710 (1999)Cite this article

Skeletal muscle is a likely site for the delivery and expression of exogenous genes, both to treat local diseases and to act as a 'bioreactor' for producing therapeutic proteins to treat systemic diseases1,2,3,4,5,6,7,8,9. Plasmid DNA-based gene delivery vehicles, unlike viral ones, do not require foreign accessory proteins for delivery of DNA into cells or tissue, thereby avoiding the strong local inflammatory response as well as the systemic humoral and cellular immune responses that may reduce the therapeutic potential of viral vectors. Despite these advantages, however, the use of plasmid DNA injection to treat diseases has been precluded by the finding that plasmid DNA is inefficiently taken up by muscle cells and produces relatively low-level and short-term expression compared with viral vectors.

Embedding of plasmid DNA in the Minipellet

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Figure 1: Cumulative release profiles of plasmid DNA from the Minipellet.
Figure 2: Time course of platelet count in mice with the Minipellet containing plasmid DNA.
Figure 3: Kinetic analysis of the serum HST-1/FGF-4 protein concentration.
Figure 4: Human HST-1/FGF-4 content in mice muscles.
Figure 5: PCR analysis of total blood DNA after injection of the Minipellet.
Figure 6: Localization of plasmid DNA after injection of the Minipellet.

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Acknowledgements

We thank M. Abe for technical assistance. This work was supported in part by a Grant-in-Aid for the Second Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare, by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare in Japan, and by the Sagawa Foundation for Promotion of Cancer Research.

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Authors and Affiliations

  1. National Cancer Center Research Institute, 1-1, Tsukiji, 5-chome, Chuo-ku, 104 , Tokyo, Japan

    Takahiro Ochiya, Yasushi Takahama & Masaaki Terada

  2. Manufacturing Technology Research Laboratories Sumitomo Pharmaceuticals Co., Ltd., 3-45 Kurakakiuchi 1-chome, Ibaraki-shi, 567, Osaka, Japan

    Shunji Nagahara & Akihiko Hisada

  3. Discovery Research Laboratories III, Research Center, Sumitomo Pharmaceuticals Co., Ltd., 3-45 Kurakakiuchi 1-chome , Ibaraki-shi, 567, Osaka, Japan

    Yoshihiro Sumita

  4. Koken Bioscience Institute, 2-6, Okubo 2-chome, Shinjuku-ku, 169, Tokyo, Japan

    Hiroshi Itoh & Yutaka Nagai

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  1. Takahiro Ochiya
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Correspondence to Masaaki Terada.

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Ochiya, T., Takahama, Y., Nagahara, S. et al. New delivery system for plasmid DNA in vivo using atelocollagen as a carrier material: the Minipellet. Nat Med 5, 707–710 (1999). https://doi.org/10.1038/9560

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