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 journalArticlepeer-review

218 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

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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