Start codon disruption with CRISPR/Cas9 prevents murine Fuchs' endothelial corneal dystrophy
Document Type
Journal ArticlePublication Date
2021-06-08Keywords
AdenovirusCRISPR/Cas9
Fuchs endothelial corneal dystrophy
genetics
genomics
human
mouse
off-target analysis of CRISPR/Cas9
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Eye Diseases
Genetics and Genomics
Ophthalmology
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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 of corneal endothelial cells. We demonstrate that CRISPR/Cas9-based postnatal gene editing achieves structural and functional rescue in a mouse model of FECD. A single intraocular injection of an adenovirus encoding both the Cas9 gene and guide RNA (Ad-Cas9-Col8a2gRNA) efficiently knocked down mutant COL8A2 expression in corneal endothelial cells, prevented endothelial cell loss, and rescued corneal endothelium pumping function in adult Col8a2 mutant mice. There were no adverse sequelae on histology or electroretinography. Col8a2 start codon disruption represents a non-surgical strategy to prevent vision loss in early-onset FECD. As this demonstrates the ability of Ad-Cas9-gRNA to restore the phenotype in adult post-mitotic cells, this method may be widely applicable to adult-onset diseases, even in tissues affected with disorders of non-reproducing cells.Source
Uehara H, Zhang X, Pereira F, Narendran S, Choi S, Bhuvanagiri S, Liu J, Ravi Kumar S, Bohner A, Carroll L, Archer B, Zhang Y, Liu W, Gao G, Ambati J, Jun AS, Ambati BK. Start codon disruption with CRISPR/Cas9 prevents murine Fuchs' endothelial corneal dystrophy. Elife. 2021 Jun 8;10:e55637. doi: 10.7554/eLife.55637. PMID: 34100716; PMCID: PMC8216720. Link to article on publisher's site
DOI
10.7554/eLife.55637Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41971PubMed ID
34100716Notes
Full author list omitted for brevity. For the full list of authors, see article.
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Copyright © 2021, Uehara et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.55637
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Except where otherwise noted, this item's license is described as Copyright © 2021, Uehara et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.