biostudies-literatureUnknown23Argyriou CFonds de recherche du Québec SantéGlobal Foundation for Peroxisomal DisordersCanadian Institutes of Health ResearchPatients with Zellweger spectrum disorder (ZSD) commonly present with vision loss due to mutations in <i>PEX</i> genes required for peroxisome assembly and function. Here, we evaluate <i>PEX1</i> retinal gene augmentation therapy in a mouse model of mild ZSD bearing the murine equivalent (PEX1-p[Gly844Asp]) of the most common human mutation. Experimental adeno-associated virus 8.cytomegalovirus.human PEX1.hemagglutinin (AAV8.CMV.<i>HsPEX1.HA</i>) and control AAV8.CMV.<i>EGFP</i> vectors were administered by subretinal injection in contralateral eyes of early (5-week-old)- or later (9-week-old)-stage retinopathy cohorts. HsPEX1.HA protein was expressed in the retina with no gross histologic side effects. Peroxisomal metabolic functions, assessed by retinal C26:0 lysophosphatidylcholine (lysMolecular therapy. Methods & clinical development225-240https://www.ebi.ac.uk/biostudies/studies/S-EPMC8516995biostudies-literatureAAV-mediated <i>PEX1</i> gene augmentation improves visual function in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder.PMC8516995Braverman NEOmri SArgyriou CHacia JGDi Pietro EBennett JSteele BSong JYMcDougald DSLachapelle PBouchard JFPolosa ACecyre BfalseAAV-mediated <i>PEX1</i> gene augmentation improves visual function in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder.Patients with Zellweger spectrum disorder (ZSD) commonly present with vision loss due to mutations in <i>PEX</i> genes required for peroxisome assembly and function. Here, we evaluate <i>PEX1</i> retinal gene augmentation therapy in a mouse model of mild ZSD bearing the murine equivalent (PEX1-p[Gly844Asp]) of the most common human mutation. Experimental adeno-associated virus 8.cytomegalovirus.human PEX1.hemagglutinin (AAV8.CMV.<i>HsPEX1.HA</i>) and control AAV8.CMV.<i>EGFP</i> vectors were administered by subretinal injection in contralateral eyes of early (5-week-old)- or later (9-week-old)-stage retinopathy cohorts. HsPEX1.HA protein was expressed in the retina with no gross histologic side effects. Peroxisomal metabolic functions, assessed by retinal C26:0 lysophosphatidylcholine (lys2021-01-01T00:00:00Z2021 Dec2026-05-07T22:24:54.093Z2025-04-19T08:23:17.901ZS-EPMC85169953470384410.1016/j.omtm.2021.09.002