Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems

Ken Y. Chan, Min J. Jang, Bryan B. Yoo, Alon Greenbaum, Namita Ravi, Wei-Li Wu, Luis Sánchez-Guardado, Carlos Lois, Sarkis K. Mazmanian, Benjamin E. Deverman, Viviana Gradinaru

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Adeno-associated viruses (AAVs) are commonly used for in vivo gene transfer. Nevertheless, AAVs that provide efficient transduction across specific organs or cell populations are needed. Here, we describe AAV-PHP.eB and AAV-PHP.S, capsids that efficiently transduce the central and peripheral nervous systems, respectively. In the adult mouse, intravenous administration of 1 × 10 11 vector genomes (vg) of AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons, while 1 × 10 12 vg of AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons. The efficiency of these vectors facilitates robust cotransduction and stochastic, multicolor labeling for individual cell morphology studies. To support such efforts, we provide methods for labeling a tunable fraction of cells without compromising color diversity. Furthermore, when used with cell-type-specific promoters and enhancers, these AAVs enable efficient and targetable genetic modification of cells throughout the nervous system of transgenic and non-transgenic animals.

Original languageEnglish
Pages (from-to)1172-1179
Number of pages8
JournalNature Neuroscience
Volume20
Issue number8
DOIs
Publication statusPublished - 2017 Aug 1

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Dependovirus
Peripheral Nervous System
Central Nervous System
Genes
Neurons
Genome
Corpus Striatum
Capsid
Spinal Ganglia
Intravenous Administration
Nervous System
Color
Population

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Chan, K. Y., Jang, M. J., Yoo, B. B., Greenbaum, A., Ravi, N., Wu, W-L., ... Gradinaru, V. (2017). Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nature Neuroscience, 20(8), 1172-1179. https://doi.org/10.1038/nn.4593
Chan, Ken Y. ; Jang, Min J. ; Yoo, Bryan B. ; Greenbaum, Alon ; Ravi, Namita ; Wu, Wei-Li ; Sánchez-Guardado, Luis ; Lois, Carlos ; Mazmanian, Sarkis K. ; Deverman, Benjamin E. ; Gradinaru, Viviana. / Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. In: Nature Neuroscience. 2017 ; Vol. 20, No. 8. pp. 1172-1179.
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Chan, KY, Jang, MJ, Yoo, BB, Greenbaum, A, Ravi, N, Wu, W-L, Sánchez-Guardado, L, Lois, C, Mazmanian, SK, Deverman, BE & Gradinaru, V 2017, 'Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems', Nature Neuroscience, vol. 20, no. 8, pp. 1172-1179. https://doi.org/10.1038/nn.4593

Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. / Chan, Ken Y.; Jang, Min J.; Yoo, Bryan B.; Greenbaum, Alon; Ravi, Namita; Wu, Wei-Li; Sánchez-Guardado, Luis; Lois, Carlos; Mazmanian, Sarkis K.; Deverman, Benjamin E.; Gradinaru, Viviana.

In: Nature Neuroscience, Vol. 20, No. 8, 01.08.2017, p. 1172-1179.

Research output: Contribution to journalArticle

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