Prime editing for the investigation of aberrant splicing defect associated with a pathogenic <i>PRPH2</i> variant.

ABSTRACT: The human Peripherin 2 (PRPH2) gene, essential for the structure and function of photoreceptor outer segments, is implicated in a range of inherited retinal diseases (IRDs). This study focuses on the pathogenic c.828+1G>A PRPH2 splice site variant. We employed prime editing (PE) technology to install and correct this variant in human induced pluripotent stem cells (hiPSCs). We developed an all-in-one PE construct, featuring a GFP reporter to facilitate the identification of successfully edited clones. The resulting heterozygous and homozygous hiPSC clones exhibited no detectable off-target mutations or karyotype abnormalities. Crucially, we found in hiPSCs and DD50/DD100 precursor hiPSC-derived retinal organoids that the c.828+1G>A PRPH2 mutation leads to activation of

SUBMITTER: Lopes da Costa B 

PROVIDER: S-EPMC12594906 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature