Gene augmentation prevents retinal degeneration in a CRISPR/Cas9-based mouse model of PRPF31 retinitis pigmentosa
Data files
Oct 19, 2022 version files 265.51 MB
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1OD_S2_L001_R1_001.fastq.gz
4.70 MB
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1OD_S2_L001_R2_001.fastq.gz
5.10 MB
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1OS_S5_L001_R1_001.fastq.gz
6.38 MB
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1OS_S5_L001_R2_001.fastq.gz
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2OD_S1_L001_R1_001.fastq.gz
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2OD_S1_L001_R2_001.fastq.gz
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2OS_S3_L001_R1_001.fastq.gz
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2OS_S3_L001_R2_001.fastq.gz
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3OD_S4_L001_R1_001.fastq.gz
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3OD_S4_L001_R2_001.fastq.gz
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3OS_S6_L001_R1_001.fastq.gz
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3OS_S6_L001_R2_001.fastq.gz
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5wCas9IVT-1_S7_L001_R1_001.fastq.gz
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5wCas9IVT-1_S7_L001_R2_001.fastq.gz
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5wCas9IVT-2_S1_L001_R1_001.fastq.gz
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5wCas9IVT-2_S1_L001_R2_001.fastq.gz
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5wCas9IVT-3_S2_L001_R1_001.fastq.gz
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5wCas9IVT-3_S2_L001_R2_001.fastq.gz
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5wCas9SRi-1_S5_L001_R1_001.fastq.gz
10.09 MB
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5wCas9SRi-1_S5_L001_R2_001.fastq.gz
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5wCas9SRi-2_S6_L001_R1_001.fastq.gz
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5wCas9SRi-2_S6_L001_R2_001.fastq.gz
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5wCas9SRi-3_S3_L001_R1_001.fastq.gz
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5wCas9SRi-3_S3_L001_R2_001.fastq.gz
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5wgh-5OS_S8_L001_R1_001.fastq.gz
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5wgh-5OS_S8_L001_R2_001.fastq.gz
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5wgh-6OS_S4_L001_R1_001.fastq.gz
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5wgh-6OS_S4_L001_R2_001.fastq.gz
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5wgh-7OS_S1_L001_R1_001.fastq.gz
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5wgh-7OS_S1_L001_R2_001.fastq.gz
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7ab-1_S3_R1.cutadapt.fastq.gz
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7ab-1_S3_R2.cutadapt.fastq.gz
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7ab-2_S4_R1.cutadapt.fastq.gz
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7ab-2_S4_R2.cutadapt.fastq.gz
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7ab-3_S2_R1.cutadapt.fastq.gz
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7ab-3_S2_R2.cutadapt.fastq.gz
2.79 MB
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7ab-4_S1_R1.cutadapt.fastq.gz
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7ab-4_S1_R2.cutadapt.fastq.gz
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README.txt
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Abstract
Mutations in PRPF31 cause autosomal dominant retinitis pigmentosa, an untreatable form of blindness. Gene therapy is a promising treatment for PRPF31-retinitis pigmentosa, however, there are currently no suitable animal models in which to develop AAV-mediated gene augmentation. Here we establish Prpf31 mutant mouse models using AAV-mediated CRISPR/Cas9 knockout, and characterize the resulting retinal degeneration phenotype. Mouse models with early-onset morphological and functional impairments like those in patients were established, providing new platforms in which to investigate pathogenetic mechanisms and develop therapeutic methods. AAV-mediated PRPF31 gene augmentation restored the retinal structure and function in a rapidly degenerating mouse model, demonstrating the first in vivo proof-of-concept for AAV-mediated gene therapy to treat PRPF31-retinitis pigmentosa. AAV-CRISPR/Cas9-PRPF31 knockout constructs also mediated efficient PRPF31 knockout in human and non-human primate retinal explants, laying a foundation for establishing non-human primate models using the method developed here.