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

Mol Ther. 2016 Mar;24(3):556-63. doi: 10.1038/mt.2015.220. Epub 2015 Dec 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Binding Sites
  • CRISPR-Cas Systems*
  • Gene Editing*
  • Gene Order
  • Genetic Therapy
  • Genetic Vectors / genetics
  • Humans
  • Mutation
  • Phenotype
  • Photoreceptor Cells, Vertebrate / metabolism
  • RNA, Guide, CRISPR-Cas Systems
  • Rats
  • Retinal Dystrophies / genetics
  • Retinal Dystrophies / pathology
  • Retinal Dystrophies / therapy
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology*
  • Retinitis Pigmentosa / therapy
  • Synapses / metabolism
  • rho GTP-Binding Proteins / genetics*

Substances

  • RNA, Guide, CRISPR-Cas Systems
  • rho GTP-Binding Proteins