Cell type-specific transgene expression in mice has broad utility in biomedical research. We developed a versatile system for in vivo transgene delivery using adeno-associated virus (AAV). Efficient and tissue-specific transgene expression is achieved by regulating the expression of the gene encoding the AAV receptor, thereby precisely targeting AAV to the cell type of interest.
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References
Gurumurthy, C. B., Saunders, T. L. & Ohtsuka, M. Designing and generating a mouse model: frequently asked questions. J. Biomed. Res. 35, 76–90 (2021). This paper shows traditional methods of generating transgenic mouse models.
Haery, L. et al. Adeno-associated virus technologies and methods for targeted neuronal manipulation. Front. Neuroanat. 13, 93 (2019). This paper shows how AAV can be used to target certain cells, with a focus on neuronal targeting.
Pillay, S. et al. An essential receptor for adeno-associated virus infection. Nature 530, 108–112 (2016). This paper identified the receptor for AAV and other host factors important for viral entry and gene expression.
Chan, K. Y. et al. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat. Neurosci. 20, 1172–1179 (2017). This paper identifies AAV capsid variants that can target the nervous system — specifically, the one that can cross the blood–brain barrier that we used in our study.
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This is a summary of: Zengel, J. et al. Hardwiring tissue-specific AAV transduction in mice through engineered receptor expression. Nat. Methods https://doi.org/10.1038/s41592-023-01896-x (2023).
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A flexible system for tissue-specific gene expression in mice using adeno-associated virus. Nat Methods 20, 997–998 (2023). https://doi.org/10.1038/s41592-023-01897-w
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DOI: https://doi.org/10.1038/s41592-023-01897-w