Abstract: Described herein are methods and compositions for genomic editing. Clustered regularly interspaced short palindromic (CRISPR) allows for highly selective targeting and alteration of genetic loci. Here, the Inventors demonstrate CRISPR as capable of being used in living animals to prophylactically prevent a genetic disease from manifesting. Targeting and disruption of mutated rhodopsin gene prevents progression of retinitis pigmentosa in the retinal cells of a transgenic rat model. Such techniques allow for treatment methods in subjects with dominant genetic mutations, often associated with lack of a gene product, or a toxic gene product. The described technology effectively abrogates deleterious effects due to the presence of a mutated gene copy allowing the normal function of the wild-type protein to prevent cell and vision loss. The efficacy of these in vivo mechanisms are widely extensible to similar dominant negative gene mutations causing disease, or other types of genetic disease.