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Altering Entry Site Preference of Lentiviral Vectors into Neuronal Cells by Pseudotyping with Envelope Glycoproteins

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Gene Therapy for Neurological Disorders

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1382))

Abstract

A lentiviral vector system provides a powerful strategy for gene therapy trials against a variety of neurological and neurodegenerative disorders. Pseudotyping of lentiviral vectors with different envelope glycoproteins not only confers the neurotropism to the vectors, but also alters the preference of sites of vector entry into neuronal cells. One major group of lentiviral vectors is a pseudotype with vesicular stomatitis virus glycoprotein (VSV-G) that enters preferentially cell body areas (somata/dendrites) of neurons and transduces them. Another group contains lentiviral vectors pseudotyped with fusion envelope glycoproteins composed of different sets of rabies virus glycoprotein and VSV-G segments that enter predominantly axon terminals of neurons and are transported through axons retrogradely to their cell bodies, resulting in enhanced retrograde gene transfer. This retrograde gene transfer takes a considerable advantage of delivering the transgene into neuronal cell bodies situated in regions distant from the injection site of the vectors. The rational use of these two vector groups characterized by different entry mechanisms will further extend the strategy for gene therapy of neurological and neurodegenerative disorders.

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Authors and Affiliations

  1. Section of Viral Vector Development, National Institute of Physiological Sciences, Okazaki, 444-8585, Japan

    Kenta Kobayashi

  2. Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan

    Shigeki Kato & Kazuto Kobayashi

  3. Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, 484-8506, Japan

    Ken-ichi Inoue & Masahiko Takada

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  1. Kenta Kobayashi
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  2. Shigeki Kato
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  3. Ken-ichi Inoue
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  4. Masahiko Takada
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  5. Kazuto Kobayashi
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Correspondence to Kazuto Kobayashi .

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  1. Translational Science and Molecular Medicine, Michigan State University, College of Human Science, Grand Rapids, Michigan, USA

    Fredric P. Manfredsson

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Kobayashi, K., Kato, S., Inoue, Ki., Takada, M., Kobayashi, K. (2016). Altering Entry Site Preference of Lentiviral Vectors into Neuronal Cells by Pseudotyping with Envelope Glycoproteins. In: Manfredsson, F. (eds) Gene Therapy for Neurological Disorders. Methods in Molecular Biology, vol 1382. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3271-9_12

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  • DOI: https://doi.org/10.1007/978-1-4939-3271-9_12

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3270-2

  • Online ISBN: 978-1-4939-3271-9

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