Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model

DOI Web Site 被引用文献1件
  • Li Jiang
    Departments of aOphthalmology and Visual Sciences and
  • Houbin Zhang
    Departments of aOphthalmology and Visual Sciences and
  • Alexander M. Dizhoor
    Department of Basic Sciences and Pennsylvania College of Optometry, Salus University, Elkins Park, PA 19027;
  • Shannon E. Boye
    Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL 32610; and
  • William W. Hauswirth
    Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL 32610; and
  • Jeanne M. Frederick
    Departments of aOphthalmology and Visual Sciences and
  • Wolfgang Baehr
    Departments of aOphthalmology and Visual Sciences and

抄録

<jats:p>RNA interference (RNAi) gene silencing is a potential therapeutic strategy for dominant retinal degeneration disorders. We used self-complementary (sc) AAV2/8 vector to develop an RNAi-based gene therapy in a dominant retinal degeneration mouse model expressing bovine GCAP1(Y99C). We established an in vitro shRNA screening assay based on EGFP-tagged bovine GCAP1, and identified a shRNA that effectively silenced the bovine GCAP1 transgene with ∼80% efficiency. Subretinal injection of scAAV2/8 carrying shRNA expression cassette showed robust expression as early as 1 wk after injection. The gene silencing significantly improved photoreceptor survival, delayed disease onset, and increased visual function. Our results provide a promising strategy toward effective RNAi-based gene therapy by scAAV2/8 delivery for dominant retinal diseases.</jats:p>

収録刊行物

被引用文献 (1)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ