Neutralizing Antibody Evasion Ability of Adenovirus Vector Induced by the Bioconjugation of Methoxypolyethylene Glycol Succinimidyl Propionate (MPEG-SPA)

  • Eto Yusuke
    Graduate School of Pharmaceutical Sciences, Osaka University
  • Gao Jian-Qing
    Graduate School of Pharmaceutical Sciences, Osaka University Department of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University
  • Sekiguchi Fumiko
    Graduate School of Pharmaceutical Sciences, Osaka University
  • Kurachi Shinnosuke
    Graduate School of Pharmaceutical Sciences, Osaka University
  • Katayama Kazufumi
    Graduate School of Pharmaceutical Sciences, Osaka University
  • Mizuguchi Hiroyuki
    Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Japan
  • Hayakawa Takao
    National Institute of Health Sciences, Japan
  • Tsutsumi Yasuo
    Graduate School of Pharmaceutical Sciences, Osaka University
  • Mayumi Tadanori
    Graduate School of Pharmaceutical Sciences, Osaka University
  • Nakagawa Shinsaku
    Graduate School of Pharmaceutical Sciences, Osaka University

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抄録

Although adenovirus vectors (Ad) which possesses high transduction efficiency are widely used for gene therapy in animal models, clinical use is very limited. One of the main reason is that nearly 80% of human beings possess anti-Ad antibodies. In this study, we tried to modify Ad with methoxypolyethylene glycol (MPEG) activated by succinimidyl propionate, and, the neutralizing antibody evasion ability of PEGylated Ad was evaluated. The results demonstrated that PEG-Ad showed stronger protection ability against anti-Ad neutralizing antibody compared to that with unmodified-Ad. Considering there are many people carrying neutralizing antibody against Ad and readministration of Ad was necessary for treating chronic diseases, this strategy, which was also applicable to other vectors, can be used for developing improved vectors.

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