Start codon disruption with CRISPR/Cas9 prevents murine Fuchs’ endothelial corneal dystrophy

A missense mutation of collagen type VIII alpha 2 chain ( COL8A2 ) gene leads to early-onset Fuchs’ endothelial corneal dystrophy (FECD), which progressively impairs vision through the loss cells. We demonstrate that CRISPR/Cas9-based postnatal editing achieves structural and functional rescue in a mouse model FECD. single intraocular injection an adenovirus encoding both Cas9 guide RNA (Ad-Cas9-Col8a2gRNA) efficiently knocked down mutant expression cells, prevented cell loss, rescued endothelium pumping function adult Col8a2 mice. There were no adverse sequelae on histology or electroretinography. start codon disruption represents non-surgical strategy prevent As this demonstrates ability Ad-Cas9-gRNA restore phenotype post-mitotic method may be widely applicable adult-onset diseases, even tissues affected with disorders non-reproducing