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Modifications of a signal sequence for antibody secretion from insect cells

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Abstract

Monoclonal antibodies and antibody fragments have recently been developed for use in diverse diagnostic and therapeutic applications. Insect cells can efficiently secrete recombinant proteins such as antibody molecules through post-translational processing and modifications that are similar to those performed in mammalian cells. In eukaryotic cells, the signal sequence in a nascent polypeptide is recognized by the signal recognition particle, and the polypeptide is then folded and modified in the endoplasmic reticulum. The signal sequence consists of three regions, a positively charged N-terminus, a hydrophobic core, and a polar C-terminus. In the present study, we examined the substitutions of the characteristic amino acids of a Drosophila immunoglobulin heavy chain binding protein signal sequence, and investigated the effect on the secretory production of an antibody Fab fragment from lepidopteran insect cells in transient expression. A modification of the signal sequence for the heavy chain resulted in a twofold increase in the secreted Fab fragment, while the modification for the light chain led to a more than 3.6-fold increase.

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Acknowledgements

This research was partially supported by the programs for developing key technologies for discovering and manufacturing pharmaceuticals used for next-generation treatments and diagnoses both from the Ministry of Economy, Trade and Industry, Japan (METI) and from the Japan Agency for Medical Research and Development (AMED).

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Author notes

  1. Yuki Ohmuro-Matsuyama

    Present address: Laboratory for Chemistry and Life Science, Institute for Innovative Research, Tokyo Institute of Technology, Yokohama, 226–8503, Japan

Authors and Affiliations

  1. Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1–1 Rokkodai, Nada, Kobe, 657–8501, Japan

    Yuki Ohmuro-Matsuyama & Hideki Yamaji

  2. Manufacturing Technology Association of Biologics (MAB), Integrated Research Center of Kobe University, 7–1–49 Minatojima-Minamimachi, Chuo-ku, Kobe, 650–0047, Japan

    Hideki Yamaji

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  1. Yuki Ohmuro-Matsuyama
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Correspondence to Hideki Yamaji.

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Ohmuro-Matsuyama, Y., Yamaji, H. Modifications of a signal sequence for antibody secretion from insect cells. Cytotechnology 70, 891–898 (2018). https://doi.org/10.1007/s10616-017-0109-0

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