Journal
NATURE NEUROSCIENCE
Volume 20, Issue 8, Pages 1172-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4593
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Funding
- National Institutes of Health (NIH)
- Director's New Innovator [DP2NS087949]
- PECASE
- SPARC [OT2OD023848-01]
- National Institute on Aging [R01AG047664]
- BRAIN [U01NS090577]
- National Institute of Mental Health (NIMH) [R21MH103824]
- Gordon and Betty Moore Foundation [GBMF2509]
- Curd Foundation
- Hereditary Disease Foundation
- Beckman Institute
- Rosen Center at Caltech
- NIH [U01 MH109147 02S1, NS085910]
- Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office
- Friedrich's Ataxia Research Alliance (FARA)
- FARA Australasia
- Heritage Medical Research Institute
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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 x 10(11) vector genomes (vg) of AAV-PHP. eB transduced 69% of cortical and 55% of striatal neurons, while 1 x 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.
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