Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice

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 ade...

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Vydáno v:	Nature communications Ročník 8; číslo 1; s. 14716 - 15
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 14.03.2017 Nature Publishing Group Nature Portfolio
Témata:	38/1 38/70 42 42/109 45 45/23 45/70 59 59/5 631/208/4041/3196 692/699/3161/3175 Animals Basic-Leucine Zipper Transcription Factors - genetics Cell Survival - genetics CRISPR CRISPR-Cas Systems Dependovirus Disease Eye Proteins - genetics Gene Editing - methods Gene Knockdown Techniques Genes Genetic engineering Genomes Humanities and Social Sciences Kinases Mice multidisciplinary Mutation Neurosciences Photoreception Photoreceptors Retina Retinal Cone Photoreceptor Cells - cytology Retinal Cone Photoreceptor Cells - metabolism Retinal Degeneration - genetics Retinal Rod Photoreceptor Cells - cytology Retinal Rod Photoreceptor Cells - metabolism Retinitis Pigmentosa - genetics RNA polymerase Science Science (multidisciplinary) Visual acuity United States > US Maryland
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. Retinitis pigmentosa is mainly caused by mutations that initially affect survival of rod photoreceptors, leading to secondary loss of cones. Here the authors use gene editing to prevent rod degeneration, leading to survival of cones and improved vision in mice.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms14716