期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 45, 页码 18476-18481出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1112758108
关键词
human retina disease; transgenic mouse model; short hairpin RNA knockdown; rod and cone photoreceptors
资金
- National Institutes of Health (National Eye Institute core grant) [EY08123, EY019298, EY014800-039003, EY11522, EY08571]
- Foundation Fighting Blindness, Inc.
- University of Utah
- Department of Ophthalmology at the University of Utah
- Research to Prevent Blindness
- Foundation Fighting Blindness
- Macula Vision Research Foundation
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 similar to 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据