{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Allende ML"],"funding":["Intramural NIH HHS"],"pagination":["e183434"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12352896"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["135(16)"],"pubmed_abstract":["Late-onset Tay-Sachs (LOTS) disease is a lysosomal storage disorder most commonly caused by a point mutation (c.805G>A) in the HEXA gene encoding the α subunit of the lysosomal enzyme β-hexosaminidase A. LOTS manifests as a range of gradually worsening neurological symptoms beginning in young adulthood. Here, we explored the efficacy of an adenine base editor (ABE) programmed with an sgRNA to correct the HEXA c.805G>A mutation. Base editing in fibroblasts from a patient with LOTS successfully converted the pathogenic HEXA c.805A to G and partially restored β-hexosaminidase activity, with minimal genome-wide off-target editing. We generated a LOTS mouse model in which the mice exhibited decreased β-hexosaminidase activity, accumulation of GM2 ganglioside in the brain, progressive neurologic"],"journal":["The Journal of clinical investigation"],"pubmed_title":["CNS-targeted base editing of the major late-onset Tay-Sachs mutation alleviates disease in mice."],"pmcid":["PMC12352896"],"funding_grant_id":["ZIA DK056016"],"pubmed_authors":["Lee YT","Byrnes C","Li C","Bakir JY","Allende ML","Zhu H","Olmsted SM","Tuymetova G","Pratto F","Proia RL","Kono M","Tifft CJ","Huso V"],"additional_accession":[]},"is_claimable":false,"name":"CNS-targeted base editing of the major late-onset Tay-Sachs mutation alleviates disease in mice.","description":"Late-onset Tay-Sachs (LOTS) disease is a lysosomal storage disorder most commonly caused by a point mutation (c.805G>A) in the HEXA gene encoding the α subunit of the lysosomal enzyme β-hexosaminidase A. LOTS manifests as a range of gradually worsening neurological symptoms beginning in young adulthood. Here, we explored the efficacy of an adenine base editor (ABE) programmed with an sgRNA to correct the HEXA c.805G>A mutation. Base editing in fibroblasts from a patient with LOTS successfully converted the pathogenic HEXA c.805A to G and partially restored β-hexosaminidase activity, with minimal genome-wide off-target editing. We generated a LOTS mouse model in which the mice exhibited decreased β-hexosaminidase activity, accumulation of GM2 ganglioside in the brain, progressive neurologic","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-29T16:34:25.037Z","creation":"2026-04-08T05:24:47.031Z"},"accession":"S-EPMC12352896","cross_references":{"pubmed":["40526437"],"doi":["10.1172/JCI183434"]}}