{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hammond SM"],"funding":["SMA Trust","University of Oxford Medical and Life Sciences Translation Fund","MRC-LMB/AstraZeneca/MedImmune Collaborative Blue-Sky Research Grant","UKRI Medical Research Council","Medical Research Council","Ecole de l’INSERM-Liliane Bettencourt Scholarship","Erasmus+","Muscular Dystrophy UK","University of Oxford Clarendon Fund"],"pagination":["e154142"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7614086"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(24)"],"pubmed_abstract":["Antisense oligonucleotides (ASOs) have emerged as one of the most innovative new genetic drug modalities. However, their high molecular weight limits their bioavailability for otherwise-treatable neurological disorders. We investigated conjugation of ASOs to an antibody against the murine transferrin receptor, 8D3130, and evaluated it via systemic administration in mouse models of the neurodegenerative disease spinal muscular atrophy (SMA). SMA, like several other neurological and neuromuscular diseases, is treatable with single-stranded ASOs that modulate splicing of the survival motor neuron 2 (SMN2) gene. Administration of 8D3130-ASO conjugate resulted in elevated levels of bioavailability to the brain. Additionally, 8D3130-ASO yielded therapeutic levels of SMN2 splicing in the central "],"journal":["JCI insight"],"pubmed_title":["Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy."],"pmcid":["PMC7614086"],"funding_grant_id":["N/A","MC_U105178803","MR/R025312/1","19GRO-PG36-0294"],"pubmed_authors":["Burrell M","Wood MJ","Ahlskog N","Gurrell I","Gait MJ","Goli L","Abendroth F","Stoodley J","Hammond SM","Thom G","Webster CI"],"additional_accession":[]},"is_claimable":false,"name":"Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy.","description":"Antisense oligonucleotides (ASOs) have emerged as one of the most innovative new genetic drug modalities. However, their high molecular weight limits their bioavailability for otherwise-treatable neurological disorders. We investigated conjugation of ASOs to an antibody against the murine transferrin receptor, 8D3130, and evaluated it via systemic administration in mouse models of the neurodegenerative disease spinal muscular atrophy (SMA). SMA, like several other neurological and neuromuscular diseases, is treatable with single-stranded ASOs that modulate splicing of the survival motor neuron 2 (SMN2) gene. Administration of 8D3130-ASO conjugate resulted in elevated levels of bioavailability to the brain. Additionally, 8D3130-ASO yielded therapeutic levels of SMN2 splicing in the central ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-04T02:26:04.52Z","creation":"2025-04-04T02:26:04.52Z"},"accession":"S-EPMC7614086","cross_references":{"pubmed":["36346674"],"doi":["10.1172/jci.insight.154142"]}}