Genome-editing technologies that correct specific mutations represent a transformative new approach for treating genetic disorders. Despite its widespread use in mouse models of disease, and in cell lines, the Boye lab was the first to demonstrate the effects of CRISPR/Cas9 mediated gene editing in somatic cells of non-human primate. Their results were recently published in Human Gene Therapy.
Mutations in GUCY2D, the gene encoding retinal guanylate cyclase‐1 (retGC1), are the leading cause of autosomal dominant cone‐rod dystrophy (CORD6). Significant progress towards clinical application of gene replacement therapy for Leber congenital amaurosis (LCA) due to recessive mutations in GUCY2D (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. We used Adeno associated virus (AAV)‐ delivered CRISPR/Cas9 to specifically edit/disrupt this gene’s early coding sequence in mouse and macaque photoreceptors, in‐vivo, thereby knocking out retGC1 expression, and demonstrably altering retinal function and structure. Neither pre‐existing nor induced Cas9‐specific T cell responses resulted in ocular inflammation in macaques, nor did it limit GUCY2D‐ editing. Our results show, for the first time, the ability
to perform somatic gene editing in primate using AAV‐CRISPR/Cas9 and demonstrate the viability this approach for treating inherited retinal diseases in general, and CORD6 in particular.