biostudies-literatureMcCullough KTNEI NIH HHS571-589https://www.ebi.ac.uk/biostudies/studies/S-EPMC6534089biostudies-literatureUnknown30(5)Mutations in <i>GUCY2D</i>, the gene encoding retinal guanylate cyclase-1 (retGC1), are the leading cause of autosomal dominant cone-rod dystrophy (CORD6). Significant progress toward clinical application of gene replacement therapy for Leber congenital amaurosis (LCA) due to recessive mutations in <i>GUCY2D</i> (LCA1) has been made, but a different approach is needed to treat CORD6 where gain of function mutations cause dysfunction and dystrophy. The CRISPR/Cas9 gene editing system efficiently disrupts genes at desired loci, enabling complete gene knockout or homology directed repair. Here, adeno-associated virus (AAV)-delivered CRISPR/Cas9 was used specifically to edit/disrupt this gene's early coding sequence in mouse and macaque photoreceptors <i>in vivo</i>, thereby knocking out retGCHuman gene therapySomatic Gene Editing of <i>GUCY2D</i> by AAV-CRISPR/Cas9 Alters Retinal Structure and Function in Mouse and Macaque.PMC6534089R01 EY025555T32 EY007132R01 EY024280P30 EY003039McCullough KTGloskowski SBoye SEPeterson JJSamuelsson SJiang HCalabro KGamlin PDWitherspoon CDChakraborty DFajardo DStrang CEMaeder MLBoye SLHaskett SfalseSomatic Gene Editing of <i>GUCY2D</i> by AAV-CRISPR/Cas9 Alters Retinal Structure and Function in Mouse and Macaque.Mutations in <i>GUCY2D</i>, the gene encoding retinal guanylate cyclase-1 (retGC1), are the leading cause of autosomal dominant cone-rod dystrophy (CORD6). Significant progress toward clinical application of gene replacement therapy for Leber congenital amaurosis (LCA) due to recessive mutations in <i>GUCY2D</i> (LCA1) has been made, but a different approach is needed to treat CORD6 where gain of function mutations cause dysfunction and dystrophy. The CRISPR/Cas9 gene editing system efficiently disrupts genes at desired loci, enabling complete gene knockout or homology directed repair. Here, adeno-associated virus (AAV)-delivered CRISPR/Cas9 was used specifically to edit/disrupt this gene's early coding sequence in mouse and macaque photoreceptors <i>in vivo</i>, thereby knocking out retGC2019-01-01T00:00:00Z2019 May2026-05-04T23:35:27.042Z2021-02-20T09:04:20ZS-EPMC65340893035843410.1089/hum.2018.193