Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter

Academic Article

Abstract

  • © 2014 The Authors. In 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.
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    Author List

  • Cronin T; Vandenberghe LH; Hantz P; Juttner J; Reimann A; Kacsó ÁE; Huckfeldt RM; Busskamp V; Kohler H; Lagali PS
  • Start Page

  • 1175
  • End Page

  • 1190
  • Volume

  • 6
  • Issue

  • 9