Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans

Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, e...

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Bibliographic Details
Published in:	Nature neuroscience 2019-08, Vol.22 (8), p.1345-1356
Main Authors:	Jüttner, Josephine, Szabo, Arnold, Gross-Scherf, Brigitte, Morikawa, Rei K, Rompani, Santiago B, Hantz, Peter, Szikra, Tamas, Esposti, Federico, Cowan, Cameron S, Bharioke, Arjun, Patino-Alvarez, Claudia P, Keles, Özkan, Kusnyerik, Akos, Azoulay, Thierry, Hartl, Dominik, Krebs, Arnaud R, Schübeler, Dirk, Hajdu, Rozina I, Lukats, Akos, Nemeth, Janos, Nagy, Zoltan Z, Wu, Kun-Chao, Wu, Rong-Han, Xiang, Lue, Fang, Xiao-Long, Jin, Zi-Bing, Goldblum, David, Hasler, Pascal W, Scholl, Hendrik P N, Krol, Jacek, Roska, Botond
Format:	Article
Language:	eng
Subjects:	Adenoviruses Animals Brain Combinatorial analysis Dependovirus - genetics Gene expression Gene targeting Gene Targeting - methods Gene therapy Gene transfer Gene Transfer Techniques Genetic aspects Glial cells Humans Identification and classification Macaca fascicularis Maintenance Methods Mice Mice, Inbred C57BL Neuroglia Neuroglia - virology Neuronal-glial interactions Neurons - virology Primates Promoter Regions, Genetic - genetics Recording Retina Retina - virology Viruses
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Summary:	Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that a number of these AAVs specifically target expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. We demonstrate applications for recording and stimulation, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.
ISSN:	1097-6256 1546-1726