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

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 tr

SUBMITTER: Yu W 

PROVIDER: S-EPMC5355895 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature