Back to Search
Start Over
Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model
- Source :
- Proceedings of the National Academy of Sciences. 108:18476-18481
- Publication Year :
- 2011
- Publisher :
- Proceedings of the National Academy of Sciences, 2011.
-
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.
- Subjects :
- Retinal degeneration
Genetic enhancement
Transgene
Mice, Transgenic
Biology
Real-Time Polymerase Chain Reaction
Cell Line
Small hairpin RNA
Mice
RNA interference
Retinitis pigmentosa
medicine
Animals
Humans
Gene silencing
Genes, Dominant
Multidisciplinary
Genetic Therapy
Biological Sciences
medicine.disease
Molecular biology
Guanylate Cyclase-Activating Proteins
Disease Models, Animal
Microscopy, Fluorescence
Cancer research
Cattle
RNA Interference
Expression cassette
Retinitis Pigmentosa
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 108
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....fbe3f2ee0ec47f9d4e1ceb468df29c8e