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

Kimura, K.; Nagai, Y.; Hatanaka, G.; Fang, Y.; Zheng, A.; Fujiwara, M.; Nakano, M.; Hori, Y.; Takeuchi, R.; Inagaki, M.; Minamimoto, T.; Fujita, I.; Inoue, K.-i.; Takada, M.

doi:10.1101/2021.07.18.452859

bioRxiv · 10.1101/2021.07.18.452859

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

Kimura, K.·Nagai, Y.·Hatanaka, G.·Fang, Y.·Zheng, A.·Fujiwara, M.·Nakano, M.·Hori, Y.·Takeuchi, R.·Inagaki, M.·Minamimoto, T.·Fujita, I.·Inoue, K.-i.·Takada, M.

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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 AAV vector of which capsid was composed of capsid proteins derived from the 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 the AAV1 vector) and neuron specificity (for the 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.

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Kimura, K., Nagai, Y., Hatanaka, G., Fang, Y., Zheng, A., Fujiwara, M., Nakano, M., Hori, Y., Takeuchi, R., Inagaki, M., Minamimoto, T., Fujita, I., Inoue, K.-i., Takada, M.. 2021-07-19. A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain. https://doi.org/10.1101/2021.07.18.452859

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