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A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain

Author

Listed:
  • Kei Kimura

    (Kyoto University)

  • Yuji Nagai

    (National Institutes for Quantum Science and Technology)

  • Gaku Hatanaka

    (Osaka University
    National Institute of Information and Communications Technology and Osaka University)

  • Yang Fang

    (Osaka University
    National Institute of Information and Communications Technology and Osaka University)

  • Soshi Tanabe

    (Kyoto University)

  • Andi Zheng

    (Kyoto University)

  • Maki Fujiwara

    (Kyoto University)

  • Mayuko Nakano

    (Kyoto University)

  • Yukiko Hori

    (National Institutes for Quantum Science and Technology)

  • Ryosuke F. Takeuchi

    (Osaka University
    National Institute of Information and Communications Technology and Osaka University)

  • Mikio Inagaki

    (Osaka University
    National Institute of Information and Communications Technology and Osaka University)

  • Takafumi Minamimoto

    (National Institutes for Quantum Science and Technology)

  • Ichiro Fujita

    (Osaka University
    National Institute of Information and Communications Technology and Osaka University)

  • Ken-ichi Inoue

    (Kyoto University
    PRESTO, Japan Science and Technology Agency)

  • Masahiko Takada

    (Kyoto University)

Abstract

Recent emphasis has been placed on gene transduction mediated through recombinant adeno-associated virus (AAV) vector to manipulate activity of neurons and their circuitry in the primate brain. In the present study, we created a novel vector of which capsid was composed of capsid proteins derived from both of the AAV serotypes 1 and 2 (AAV1 and AAV2). Following the injection into the frontal cortex of macaque monkeys, this mosaic vector, termed AAV2.1 vector, was found to exhibit the excellence in transgene expression (for AAV1 vector) and neuron specificity (for AAV2 vector) simultaneously. To explore its applicability to chemogenetic manipulation and in vivo calcium imaging, the AAV2.1 vector expressing excitatory DREADDs or GCaMP was injected into the striatum or the visual cortex of macaque monkeys, respectively. Our results have defined that such vectors secure intense and stable expression of the target proteins and yield conspicuous modulation and imaging of neuronal activity.

Suggested Citation

  • Kei Kimura & Yuji Nagai & Gaku Hatanaka & Yang Fang & Soshi Tanabe & Andi Zheng & Maki Fujiwara & Mayuko Nakano & Yukiko Hori & Ryosuke F. Takeuchi & Mikio Inagaki & Takafumi Minamimoto & Ichiro Fujit, 2023. "A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40436-1
    DOI: 10.1038/s41467-023-40436-1
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    References listed on IDEAS

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    1. Antoine R. Adamantidis & Feng Zhang & Alexander M. Aravanis & Karl Deisseroth & Luis de Lecea, 2007. "Neural substrates of awakening probed with optogenetic control of hypocretin neurons," Nature, Nature, vol. 450(7168), pages 420-424, November.
    2. Amy Poremba & Megan Malloy & Richard C. Saunders & Richard E. Carson & Peter Herscovitch & Mortimer Mishkin, 2004. "Species-specific calls evoke asymmetric activity in the monkey's temporal poles," Nature, Nature, vol. 427(6973), pages 448-451, January.
    3. Ken-ichi Inoue & Masahiko Takada & Masayuki Matsumoto, 2015. "Neuronal and behavioural modulations by pathway-selective optogenetic stimulation of the primate oculomotor system," Nature Communications, Nature, vol. 6(1), pages 1-7, December.
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