Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in miceopen access
- Authors
- Yu, Wenhan; Mookherjee, Suddhasil; Chaitankar, Vijender; Hiriyanna, Suja; Kim, Jung-Woong; Brooks, Matthew; Ataeijannati, Yasaman; Sun, Xun; Dong, Lijin; Li, Tiansen; Swaroop, Anand; Wu, Zhijian
- Issue Date
- Mar-2017
- Publisher
- NATURE PORTFOLIO
- Citation
- NATURE COMMUNICATIONS, v.8
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 8
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/52726
- DOI
- 10.1038/ncomms14716
- ISSN
- 2041-1723
- Abstract
- In retinitis pigmentosa, loss of cone photoreceptors leads to blindness, and preservation of cone function is a major therapeutic goal. However, cone loss is thought to occur as a secondary event resulting from degeneration of rod photoreceptors. Here we report a genome editing approach in which adeno-associated virus (AAV)-mediated CRISPR/Cas9 delivery to postmitotic photoreceptors is used to target the Nrl gene, encoding for Neural retina-specific leucine zipper protein, a rod fate determinant during photoreceptor development. Following Nrl disruption, rods gain partial features of cones and present with improved survival in the presence of mutations in rod-specific genes, consequently preventing secondary cone degeneration. In three different mouse models of retinal degeneration, the treatment substantially improves rod survival and preserves cone function. Our data suggest that CRISPR/Cas9-mediated NRL disruption in rods may be a promising treatment option for patients with retinitis pigmentosa.
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Collections - College of Natural Sciences > Department of Life Science > 1. Journal Articles
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