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

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 Fujita, Ken-ichi Inoue () and Masahiko Takada ()
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Kei Kimura: Kyoto University
Yuji Nagai: National Institutes for Quantum Science and Technology
Gaku Hatanaka: Osaka University
Yang Fang: 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
Mikio Inagaki: Osaka University
Takafumi Minamimoto: National Institutes for Quantum Science and Technology
Ichiro Fujita: Osaka University
Ken-ichi Inoue: Kyoto University
Masahiko Takada: Kyoto University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40436-1

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