biostudies-literatureUnknown6(1)Leclerc DGanglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in <i>GLB1</i> gene. These variants result in reduced β-galactosidase (β-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the <i>GLB1</i> gene to stop disease progression. In this study, we show that 41% of <i>GLB1</i> pathogenic SNVs can be replaced by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring therapeutic levels of β-gal activity. Off-target DNA analysis did not detect off-target editing activity in treated patient's cells, except a bystander edit without consequences on β-gal activity based on 3D structure bioinformatics predictions. Altogether, our results suggest that gene editing might be an alternative strategy to cure GM1 gangliosidosis.The CRISPR journal17-31https://www.ebi.ac.uk/biostudies/studies/S-EPMC9986017biostudies-literatureGene Editing Corrects <i>In Vitro</i> a G > A <i>GLB1</i> Transition from a GM1 Gangliosidosis Patient.PMC9986017Dreano SDubourg CEriksson LAJaillard SLevade TBelaud-Rotureau MAGuillory XMouriaux FLaunay EFroissart RLeclerc DCluzeau LOdent SEtcheverry ANouyou BDamaj LGilot DGoujon LfalseGene Editing Corrects <i>In Vitro</i> a G > A <i>GLB1</i> Transition from a GM1 Gangliosidosis Patient.Ganglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in <i>GLB1</i> gene. These variants result in reduced β-galactosidase (β-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the <i>GLB1</i> gene to stop disease progression. In this study, we show that 41% of <i>GLB1</i> pathogenic SNVs can be replaced by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring therapeutic levels of β-gal activity. Off-target DNA analysis did not detect off-target editing activity in treated patient's cells, except a bystander edit without consequences on β-gal activity based on 3D structure bioinformatics predictions. Altogether, our results suggest that gene editing might be an alternative strategy to cure GM1 gangliosidosis.2023-01-01T00:00:00Z2023 Feb2026-05-29T05:30:59.336Z2025-02-18T23:45:00.622ZS-EPMC99860173662984510.1089/crispr.2022.0045