| First Author | Jiang L | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 45 | Pages | 18476-81 |
| PubMed ID | 22042849 | Mgi Jnum | J:180234 |
| Mgi Id | MGI:5305885 | Doi | 10.1073/pnas.1112758108 |
| Citation | Jiang L, et al. (2011) Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model. Proc Natl Acad Sci U S A 108(45):18476-81 |
| abstractText | 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 approximately 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. |
