Mouse gamma-Synuclein Promoter-Mediated Gene Expression and Editing in Mammalian Retinal Ganglion Cells

Qizhao Wang, Pei Zhuang, Haoliang Huang, Liang Li, Liang Liu, Hannah C. Webber, Roopa Dalal, Leonard Siew, Clarisse M. Fligor, Kun Che Chang, Michael Nahmou, Alexander Kreymerman, Yang Sun, Jason S. Meyer, Jeffrey Louis Goldberg, Yang Hu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Optic neuropathies are a group of optic nerve (ON) diseases caused by various insults including glaucoma, inflammation, ischemia, trauma and genetic deficits, which are characterized by retinal ganglion cell (RGC) death and ON degeneration. An increasing number of genes involved in RGC intrinsic signaling have been found to be promising neural repair targets that can potentially be modulated directly by gene therapy, if we can achieve RGC specific gene targeting. To address this challenge, we first used adeno associated virus (AAV)-mediated gene transfer to perform a low throughput in vivo screening in both male and female mouse eyes and identified the mouse γ-synuclein (mSncg) promoter, which specifically and potently sustained transgene expression in mouse RGCs and also works in human RGCs. We further demonstrated that gene therapy that combines AAV-mSncg promoter with CRISPR/Cas9 gene editing can knockdown pro-degenerative genes in RGCs and provide effective neuroprotection in optic neuropathies.

Original languageEnglish (US)
JournalJournal of Neuroscience
Volume40
Issue number20
DOIs
StatePublished - May 13 2020

ASJC Scopus subject areas

  • Neuroscience(all)

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