{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6(1)"],"submitter":["Leclerc D"],"pubmed_abstract":["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."],"journal":["The CRISPR journal"],"pagination":["17-31"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9986017"],"repository":["biostudies-literature"],"pubmed_title":["Gene Editing Corrects <i>In Vitro</i> a G > A <i>GLB1</i> Transition from a GM1 Gangliosidosis Patient."],"pmcid":["PMC9986017"],"pubmed_authors":["Dreano S","Dubourg C","Eriksson LA","Jaillard S","Levade T","Belaud-Rotureau MA","Guillory X","Mouriaux F","Launay E","Froissart R","Leclerc D","Cluzeau L","Odent S","Etcheverry A","Nouyou B","Damaj L","Gilot D","Goujon L"],"additional_accession":[]},"is_claimable":false,"name":"Gene Editing Corrects <i>In Vitro</i> a G > A <i>GLB1</i> Transition from a GM1 Gangliosidosis Patient.","description":"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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-05-29T05:30:59.336Z","creation":"2025-02-18T23:45:00.622Z"},"accession":"S-EPMC9986017","cross_references":{"pubmed":["36629845"],"doi":["10.1089/crispr.2022.0045"]}}