Cronin, ThereseVandenberghe, LukHantz, PéterJuttner, JosephineReimann, AndreasKacsó, Ágota–EnikőHuckfeldt, Rachel MBusskamp, VolkerKohler, HubertusLagali, Pamela SRoska, BotondBennett, Jean2014-12-022014Cronin, T., L. H. Vandenberghe, P. Hantz, J. Juttner, A. Reimann, Á. Kacsó, R. M. Huckfeldt, et al. 2014. “Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter.” EMBO Molecular Medicine 6 (9): 1175-1190. doi:10.15252/emmm.201404077. http://dx.doi.org/10.15252/emmm.201404077.1757-4676http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454822In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON-bipolar cells light-sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON-bipolar cells. This evokes high-frequency (∼100 Hz) spiking responses in ganglion cells of previously blind, rd1, mice. Our vector is a promising vehicle for further development toward potential clinical use.en-USadeno-associated viruscapsid librarymulti-electrode arrayoptogeneticspromoter optimizationJournal Article2014-12-0210.15252/emmm.201404077