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CRISPRi mediated treatment of dominant rhodopsin-associated retinitis pigmentosa.

GSE244786 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2024/03/28 Platform GPL24676
Summary
Rhodopsin (RHO) mutations such as Pro23His, are the leading cause of dominantly inherited retinitis pigmentosa in North America. As with other dominant retinal dystrophies, these mutations lead to production of a toxic protein product, and treatment will require knockdown of the mutant allele. The purpose of this study was to develop a CRISPR-Cas9-mediated transcriptional repression strategy using catalytically inactive S. aureus Cas9 (dCas9) fused to the Krüppel-associated box (KRAB) transcriptional repressor domain. Using a reporter construct carrying GFP cloned downstream of the RHO promoter fragment (nucleotides -1403 to +73), we demonstrate a ~74%-84% reduction in RHO promoter activity in RHOpCRISPRi treated vs plasmid only controls. Following subretinal transduction of human retinal explants and transgenic Pro23His mutant pigs, significant knockdown of rhodopsin protein was achieved. Suppression of mutant transgene in vivo was associated with a reduction in ER-stress and apoptosis markers and preservation of photoreceptor cell layer thickness.
Published in
CRISPRi-Mediated Treatment of Dominant Rhodopsin-Associated Retinitis Pigmentosa
Burnight ER, Wiley LA, Mullin NK et al. · The CRISPR journal 2023 · PMID 38108516 · doi:10.1089/crispr.2023.0039
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Direct links to NCBI, no account and no request form: the whole study as GSE244786_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1024894 and SRA study SRP464857. Searching any of these in the dataset finder brings you back here.

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