Gene augmentation prevents retinal degeneration in a CRISPR/Cas9-based mouse model of PRPF31 retinitis pigmentosa
Cite this dataset
Xi, Zhouhuan et al. (2022). Gene augmentation prevents retinal degeneration in a CRISPR/Cas9-based mouse model of PRPF31 retinitis pigmentosa [Dataset]. Dryad. https://doi.org/10.5061/dryad.bcc2fqzf1
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.
Funding
National Institute of Mental Health, Award: UG3MH120094
National Eye Institute, Award: R01EY030991
Foundation Fighting Blindness
UPMC Immune Transplant and Therapy Center
China Scholarship Council
Third Xiangya Hospital, Xiangya School of Medicine
National Institutes of Health, Award: P30 EY08098
Research to Prevent Blindness, Award: Career Development Award
Foundation Fighting Blindness, Award: Individual Investigator Award
Eye and Ear Foundation of Pittsburgh