In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa

被引：247

作者：

Bakondi, Benjamin ^{[1
]}

Lv, Wenjian ^{[1
,2
]}

Lui, Bin ^{[1
]}

Jones, Melissa K. ^{[1
]}

Tsai, Yuchun ^{[1
]}

Kim, Kevin J. ^{[1
]}

Levy, Rachelle ^{[1
]}

Akhtar, Aslam Abbasi ^{[1
]}

Breunig, Joshua J. ^{[1
]}

Svendseni, Clive N. ^{[1
]}

Wang, Shaomei ^{[1
]}

机构：

[1] Cedars Sinai Med Ctr, Dept Biomed Sci, Board Governors Regenerat Med Inst, Los Angeles, CA 90048 USA

[2] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

来源：

MOLECULAR THERAPY | 2016年 / 24卷 / 03期

关键词：

RHODOPSIN; PHOTORECEPTOR; THERAPY; CRISPR-CAS9; MECHANISMS; EXPRESSION; VISION;

D O I：

10.1038/mt.2015.220

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Reliable genome editing via Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 may provide a means to correct inherited diseases in patients. As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (Rho(S334)) in rats that model severe autosomal dominant retinitis pigmentosa. A single subretinal injection of guide RNA/Cas9 plasmid in combination with electroporation generated allelel-specific disruption of Rho(S334), which prevented retinal degeneration and improved visual function.

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收藏

页码：556 / 563

页数：8

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