Efficient Gene Transfer into Differentiated Human Trophoblast Cells with Adenovirus Vector Containing RGD Motif in the Fiber Protein

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  • Koizumi Naoya
    Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Japan Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University
  • Mizuguchi Hiroyuki
    Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Japan Graduate School of Pharmaceutical Sciences, Osaka University
  • Kondoh Masuo
    Graduate School of Pharmaceutical Sciences, Osaka University Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University
  • Fujii Makiko
    Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University
  • Nakanishi Tsuyoshi
    Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University
  • Utoguchi Naoki
    Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University
  • Watanabe Yoshiteru
    Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University

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Previously we reported fiber-modified adenovirus (Ad) vectors containing the Arg-Gly-Asp (RGD) motif on the HI loop of the fiber knob (Ad-RGD vectors) have high gene transfer efficacy into some human trophoblast cell lines. In the current study, we investigate transgene activity of Ad-RGD during differentiation of human cytotrophoblast BeWo cells into syncytiotrophoblast-like cells. Although cellular differentiation into syncytiotrophoblast cells was followed by a decrease in the coxsackievirus and adenovirus receptor levels on the cell membrane, the αVβ3 and αVβ5 integrin levels did not change. Conventional adenovirus vector had lower transduction activity in the differentiated cells than non-differentiated cells. In contrast, Ad-RGD vector had no influence on differentiation and had a ca. 2—5 fold higher transduction activity than that of the conventional Ad vector. Thus, Ad-RGD vector can be a powerful tool for gene transfer experiments in syncytiotrophoblast cells.

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