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Optical Control of Mononegavirus Gene Expression and Replication

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Measles and Related Morbilliviruses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2808))

Abstract

Mononegaviruses are promising tools as oncolytic and transgene vectors for gene therapy and regenerative medicine. However, when mononegaviruses are used for therapeutic applications, the viral activity must be strictly controlled due to concerns about toxicity and severe side effects. With this technology, mononegavirus vectors can be grown where they are intended and can be easily removed when they are no longer needed. In particular, a photoswitch protein called Magnet (consisting of two magnet domains) is incorporated into the hinge region between the connector and methyltransferase domains of the mononegavirus polymerase protein (L protein) to disrupt the L protein functions. Blue light (470 ± 20 nm) irradiation causes the dimerization of the two magnet domains, and the L protein is restored to activity, allowing viral gene expression and virus replication. Since the magnet domains’ dimerization is reversible, viral gene expression and replication cease when blue light irradiation is stopped.

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Acknowledgments

The reverse genetics system for the RABV HEP-Flury strain was provided by Drs. Mutsuyo Takayama-Ito and Masayuki Saijo (Department of Virology 1, National Institute of Infectious Diseases). BHK/T7 cells and Vero/hSLAM cells were provided by Drs. Naoto Ito (Gifu University) and Yusuke Yanagi (Kyushu University), respectively. This study was supported by grants from JSPS under grant number 19K07768 to M. Tahara, 22K08616 to TO, and 21H02744 to M. Takeda, grants from the Naito Foundation and Research Foundation for Opto-Science and Technology to M. Takeda, and grant from the Japan Agency for Medical Research and Development (AMED) under grant number 23wm0325063 to M. Takeda.

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Author notes

  1. Maino Tahara and Takashi Okura are equally contributed to this work.

Authors and Affiliations

  1. Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan

    Maino Tahara & Takashi Okura

  2. Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan

    Moritoshi Sato

  3. Department of Microbiology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Makoto Takeda

Authors
  1. Maino Tahara
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  2. Takashi Okura
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  3. Moritoshi Sato
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  4. Makoto Takeda
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Corresponding author

Correspondence to Makoto Takeda .

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Editors and Affiliations

  1. Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA

    Dzwokai Z. Ma

  2. Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA

    Christian K. Pfaller

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© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Tahara, M., Okura, T., Sato, M., Takeda, M. (2024). Optical Control of Mononegavirus Gene Expression and Replication. In: Ma, D.Z., Pfaller, C.K. (eds) Measles and Related Morbilliviruses. Methods in Molecular Biology, vol 2808. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3870-5_4

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  • DOI: https://doi.org/10.1007/978-1-0716-3870-5_4

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3869-9

  • Online ISBN: 978-1-0716-3870-5

  • eBook Packages: Springer Protocols

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