1. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa
- Author
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Clive N. Svendsen, Aslam Abbasi Akhtar, Benjamin Bakondi, Rachelle Levy, Kevin J. Kim, Shaomei Wang, Melissa Kaye Jones, Bin Lu, YuChun Tsai, Wenjian Lv, and Joshua J. Breunig
- Subjects
rho GTP-Binding Proteins ,0301 basic medicine ,Retinal degeneration ,Genetic Vectors ,Biology ,medicine.disease_cause ,03 medical and health sciences ,Genome editing ,Gene Order ,Retinal Dystrophies ,Drug Discovery ,Retinitis pigmentosa ,Genetics ,medicine ,Animals ,Humans ,CRISPR ,Guide RNA ,Molecular Biology ,Alleles ,Gene Editing ,Pharmacology ,Mutation ,Binding Sites ,Cas9 ,Genetic Therapy ,medicine.disease ,Rats ,Phenotype ,030104 developmental biology ,Synapses ,Molecular Medicine ,Original Article ,CRISPR-Cas Systems ,Retinitis Pigmentosa ,Photoreceptor Cells, Vertebrate ,RNA, Guide, Kinetoplastida - Abstract
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 allele-specific disruption of Rho(S334), which prevented retinal degeneration and improved visual function.
- Published
- 2016