Publication Type |
pre-print |
School or College |
School of Medicine |
Department |
Ophthalmology |
Creator |
Frederick, Jeanne M. |
Other Author |
Jiang, Li.; Baehr, Wolfgang |
Title |
RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations |
Date |
2014-01-01 |
Description |
RNA interference (RNAi) knockdown is an efficacious therapeutic strategy for silencing genes causative for dominant retinal dystrophies. To test this, we used self-complementry (sc) AAV2/8 vector to develop an RNAi-based therapy in two dominant retinal degeneration mouse models. The allele-specific model expresses transgenic bovine GCAP1(Y99C) establishing a rapid RP-like phenotype, whereas the nonallele-specific model expressed mouse GCAP1(L151F) producing a slowly progressing cone-rod dystrophy (CORD). The late onset GCAP1(151F)-CORD mimics the dystrophy observed in human GCAP1-CORD patients. Subretinal injection of scAAV2/8 carrying shRNA expression cassettes specific for bovine or mouse guanylate cyclase-activating protein 1 (GCAP1) showed strong expression at 1 week post-injection. In both allele-specific [GCAP1(Y99C)-RP] and nonallele-specific [GCAP1(L151F)-CORD] models of dominant retinal dystrophy, RNAi-mediated gene silencing enhanced photoreceptor survival, delayed onset of degeneration and improved visual function. Such results provide a "proof of concept" toward effective RNAi-based gene therapy mediated by scAAV2/8 for dominant retinal disease based on GCAPi mutation. Further, nonallele-specific RNAi knockdown of GCApi may prove generally applicable toward the rescue of any human GCApi-based dominant cone-rod dystrophy. |
Type |
Text |
Publisher |
Frontiers Media |
Volume |
7 |
Issue |
1 |
First Page |
1 |
Last Page |
8 |
Language |
eng |
Bibliographic Citation |
Jiang, L., Frederick, J. M., & Baehr, W. (2014). RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations. Frontiers in Molecular Neuroscience, 7(1 APR), 1-8. |
Format Medium |
application/pdf |
Format Extent |
2,229,442 bytes |
Identifier |
uspace,18646 |
ARK |
ark:/87278/s6hb2f9s |
Setname |
ir_uspace |
ID |
712535 |
Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6hb2f9s |