Journal Article

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

Özkan Keles, Goldblum, David, Kusnyerik, Akos, Gross-Scherf, Brigitte, Hartl, Dominik, Szikra, Tamas, Lue Xiang, Cowan, Cameron S, Zi-Bing Jin, Krebs, Arnaud R, Rong-Han, Wu, Roska, Botond, Patino-Alvarez, Claudia P, Jüttner, Josephine, Bharioke, Arjun, Hantz, Peter, Scholl, Hendrik P N, Nemeth, Janos, Xiao-Long, Fang, Azoulay, Thierry, Hajdu, Rozina I, Esposti, Federico, Nagy, Zoltan Z, Rompani, Santiago B, Lukats, Akos, Szabo, Arnold, Hasler, Pascal W, Krol, Jacek, Schübeler, Dirk, Kun-Chao, Wu, Morikawa, Rei K

2019

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Brain / Combinatorial analysis / Gene expression / Gene therapy / Gene transfer / Glial cells / Maintenance / Neuronal-glial interactions / Primates / Recording / Retina / Viruses