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

ABSTRACT: 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.

SUBMITTER: Jiang L

PROVIDER: S-EPMC3215008 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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

Jiang Li L Zhang Houbin H Dizhoor Alexander M AM Boye Shannon E SE Hauswirth William W WW Frederick Jeanne M JM Baehr Wolfgang W

Proceedings of the National Academy of Sciences of the United States of America 20111031 45

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 car ...[more]

PMID: 22042849

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