Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice.
Nat Commun
; 8: 14716, 2017 03 14.
Article
en En
| MEDLINE
| ID: mdl-28291770
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Degeneración Retiniana
/
Supervivencia Celular
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Células Fotorreceptoras Retinianas Bastones
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Células Fotorreceptoras Retinianas Conos
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico
/
Proteínas del Ojo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos