Targeting the somatosensory system with AAV9 and AAV2retro viral vectors

利用 AAV9 和 AAV2 逆转录病毒载体靶向躯体感觉系统

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作者:Alexander G J Skorput, Reshma Gore, Rachel Schorn, Maureen S Riedl, Ezequiel Marron Fernandez de Velasco, Bailey Hadlich, Kelley F Kitto, Carolyn A Fairbanks, Lucy Vulchanova

Abstract

Adeno-associated viral (AAV) vectors allow for site-specific and time-dependent genetic manipulation of neurons. However, for successful implementation of AAV vectors, major consideration must be given to the selection of viral serotype and route of delivery for efficient gene transfer into the cell type being investigated. Here we compare the transduction pattern of neurons in the somatosensory system following injection of AAV9 or AAV2retro in the parabrachial complex of the midbrain, the spinal cord dorsal horn, the intrathecal space, and the colon. Transduction was evaluated based on Cre-dependent expression of tdTomato in transgenic reporter mice, following delivery of AAV9 or AAV2retro carrying identical constructs that drive the expression of Cre/GFP. The pattern of distribution of tdTomato expression indicated notable differences in the access of the two AAV serotypes to primary afferent neurons via peripheral delivery in the colon and to spinal projections neurons via intracranial delivery within the parabrachial complex. Additionally, our results highlight the superior sensitivity of detection of neuronal transduction based on reporter expression relative to expression of viral products.

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