{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:04:30Z","timestamp":1775617470780,"version":"3.50.1"},"reference-count":52,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy Nucleic Acids"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1016\/j.omtn.2024.102401","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T01:56:47Z","timestamp":1732586207000},"page":"102401","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective"],"prefix":"10.1016","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-9254","authenticated-orcid":false,"given":"Joshua E.","family":"Hung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reid A.","family":"Brewer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lujaina","family":"Elbakr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Mollica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgiana","family":"Forguson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wing Suen","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2132-4699","authenticated-orcid":false,"given":"Evgueni A.","family":"Ivakine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtn.2024.102401_bib1","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2015.57","article-title":"Construction of a hybrid \u03b2-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in\u00a0vivo","volume":"3","author":"Tropak","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtn.2024.102401_bib2","doi-asserted-by":"crossref","first-page":"5216","DOI":"10.1021\/bi00414a041","article-title":"Oligosaccharide structure and amino acid sequence of the major glycopeptides of mature human beta-hexosaminidase","volume":"27","author":"O\u2019dowd","year":"1988","journal-title":"Biochemistry"},{"key":"10.1016\/j.omtn.2024.102401_bib3","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1021\/bi0029200","article-title":"Identification of the 6-Sulfate Binding Site Unique to \u03b1-Subunit-Containing Isozymes of Human \u03b2-Hexosaminidase","volume":"40","author":"Sharma","year":"2001","journal-title":"Biochemistry"},{"key":"10.1016\/j.omtn.2024.102401_bib4","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.3389\/fphys.2018.01663","article-title":"New approaches to Tay-Sachs disease therapy","volume":"9","author":"Solovyeva","year":"2018","journal-title":"Front. Physiol."},{"key":"10.1016\/j.omtn.2024.102401_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0005-2760(98)00057-5","article-title":"The GM2 activator protein, its roles as a co-factor in GM2 hydrolysis and as a general glycolipid transport protein","volume":"1393","author":"Mahuran","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.omtn.2024.102401_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms21176213","article-title":"GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies","volume":"21","author":"Leal","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.omtn.2024.102401_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2021.136195","article-title":"The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment","volume":"764","author":"Toro","year":"2021","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.omtn.2024.102401_bib8","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13023-023-02637-1","article-title":"Biochemical and mutational analyses of HEXA in a cohort of Egyptian patients with infantile Tay-Sachs disease. Expansion of the mutation spectrum","volume":"18","author":"Ibrahim","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.omtn.2024.102401_bib9","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.bbrc.2010.01.088","article-title":"Rapid identification of HEXA mutations in Tay-Sachs patients","volume":"392","author":"Giraud","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.omtn.2024.102401_bib10","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1007\/BF00202478","article-title":"A null allele frequent in non-Jewish Tay-Sachs patients","volume":"90","author":"Akli","year":"1993","journal-title":"Hum. Genet."},{"key":"10.1016\/j.omtn.2024.102401_bib11","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s00439-003-1072-8","article-title":"Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: Genetic drift as a robust and parsimonious hypothesis","volume":"114","author":"Frisch","year":"2004","journal-title":"Hum. Genet."},{"key":"10.1016\/j.omtn.2024.102401_bib12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1203\/PDR.0b013e3181c6e318","article-title":"Improving accuracy of tay sachs carrier screening of the non-jewish population: Analysis of 34 carriers and six late-onset patients with hexa enzyme and dna sequence analysis","volume":"67","author":"Park","year":"2010","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.omtn.2024.102401_bib13","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1128\/MCB.21.16.5512-5519.2001","article-title":"Nonsense-Mediated Decay of Human HEXA mRNA","volume":"21","author":"Rajavel","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.omtn.2024.102401_bib14","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ymgme.2017.04.011","article-title":"Infantile Gangliosidoses: Mapping a Timeline of Clinical Changes","volume":"121","author":"Jarnes Utz","year":"2017","journal-title":"Mol. Genet. Metabol."},{"key":"10.1016\/j.omtn.2024.102401_bib15","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/ana.25689","article-title":"Natural History of Adult Patients with GM2 Gangliosidosis","volume":"87","author":"Masingue","year":"2020","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.omtn.2024.102401_bib16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1176\/jnp.10.1.10","article-title":"Neuropsychiatric aspects of the adult variant of Tay-Sachs disease","volume":"10","author":"MacQueen","year":"1998","journal-title":"J.\u00a0Neuropsychiatry Clin. Neurosci."},{"key":"10.1016\/j.omtn.2024.102401_bib17","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/BF00219337","article-title":"Quantitative correlation between the residual activity of \u03b2-hexosaminidase A and arylsulfatase A and the severity of the resulting lysosomal storage disease","volume":"88","author":"Leinekugel","year":"1992","journal-title":"Hum. Genet."},{"key":"10.1016\/j.omtn.2024.102401_bib18","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.906647","article-title":"Therapeutic Strategies For Tay-Sachs Disease","volume":"13","author":"Picache","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.omtn.2024.102401_bib19","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1080\/14712598.2022.2012148","article-title":"Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders","volume":"22","author":"Marrone","year":"2022","journal-title":"Expet Opin. Biol. Ther."},{"key":"10.1016\/j.omtn.2024.102401_bib20","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41586-019-1076-8","article-title":"Precise therapeutic gene correction by a simple nuclease-induced double-stranded break","volume":"568","author":"Iyer","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.omtn.2024.102401_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23031832","article-title":"CRISPR Therapeutics for Duchenne Muscular Dystrophy","volume":"23","author":"Erkut","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.omtn.2024.102401_bib22","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s13311-022-01197-9","article-title":"CRISPR-Cas9 Gene Therapy for Duchenne Muscular Dystrophy","volume":"19","author":"Happi Mbakam","year":"2022","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.omtn.2024.102401_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2023.122003","article-title":"Role of CRISPR\/Cas9 in the treatment of Duchenne muscular dystrophy and its delivery strategies","volume":"330","author":"Agrawal","year":"2023","journal-title":"Life Sci."},{"key":"10.1016\/j.omtn.2024.102401_bib24","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1101\/gr.250720.119","article-title":"Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation","volume":"29","author":"Erwood","year":"2019","journal-title":"Genome Res."},{"key":"10.1016\/j.omtn.2024.102401_bib25","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1136\/practneurol-2017-001665","article-title":"Late-onset Tay\u2013Sachs disease","volume":"17","author":"Barritt","year":"2017","journal-title":"Practical Neurol."},{"key":"10.1016\/j.omtn.2024.102401_bib26","first-page":"817","article-title":"Ashkenazi-Jewish and non-Jewish adult GM2 gangliosidosis patients share a common genetic defect","volume":"46","author":"Navon","year":"1990","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtn.2024.102401_bib27","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000484748","article-title":"A Chronic GM2 Gangliosidosis Variant with a HEXA Splicing Defect: Quantitation of HEXA mRNAs in Normal and Mutant Fibroblasts","volume":"5","author":"Fernandes","year":"1997","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.omtn.2024.102401_bib28","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1001\/archneur.1985.04060110058016","article-title":"Hexosaminidase-A Deficiency Presenting as Atypical Juvenile-onset Spinal Muscular Atrophy","volume":"42","author":"Parnes","year":"1985","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.omtn.2024.102401_bib29","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ymgme.2010.03.010","article-title":"Two novel exonic point mutations in HEXA identified in a juvenile Tay-Sachs patient: role of alternative splicing and nonsense-mediated mRNA decay","volume":"100","author":"Levit","year":"2010","journal-title":"Mol. Genet. Metabol."},{"key":"10.1016\/j.omtn.2024.102401_bib31","doi-asserted-by":"crossref","first-page":"9150","DOI":"10.1074\/jbc.M609304200","article-title":"Pyrimethamine as a potential pharmacological chaperone for late-onset forms of GM2 gangliosidosis","volume":"282","author":"Maegawa","year":"2007","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.omtn.2024.102401_bib30","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.mgene.2014.01.007","article-title":"The first family with Tay-Sachs disease in Cyprus: Genetic analysis reveals a nonsense (c.78G>A) and a silent (c.1305C>T) mutation and allows preimplantation genetic diagnosis","volume":"2","author":"Georgiou","year":"2014","journal-title":"Meta gene"},{"key":"10.1016\/j.omtn.2024.102401_bib32","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1038\/s41467-019-12829-8","article-title":"Genome-wide microhomologies enable precise template-free editing of biologically relevant deletion mutations","volume":"10","author":"Grajcarek","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.omtn.2024.102401_bib33","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1126\/science.aba8853","article-title":"Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants","volume":"368","author":"Walton","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.omtn.2024.102401_bib34","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jmb.2006.04.004","article-title":"Crystallographic Structure of Human \u03b2-Hexosaminidase A: Interpretation of Tay-Sachs Mutations and Loss of GM2 Ganglioside Hydrolysis","volume":"359","author":"Lemieux","year":"2006","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.omtn.2024.102401_bib35","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1091\/mbc.E16-01-0012","article-title":"Tay\u2013Sachs disease mutations in HEXA target the \u03b1 chain of hexosaminidase A to endoplasmic reticulum\u2013associated degradation","volume":"27","author":"Dersh","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.omtn.2024.102401_bib36","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.jid.2019.02.015","article-title":"Efficient Gene Reframing Therapy for Recessive Dystrophic Epidermolysis Bullosa with CRISPR\/Cas9","volume":"139","author":"Takashima","year":"2019","journal-title":"J.\u00a0Invest. Dermatol."},{"key":"10.1016\/j.omtn.2024.102401_bib37","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1080\/14728222.2022.2157258","article-title":"Early clinical and pre-clinical therapy development in Nemaline myopathy","volume":"26","author":"Fisher","year":"2022","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.omtn.2024.102401_bib38","doi-asserted-by":"crossref","first-page":"S343","DOI":"10.3233\/JND-210682","article-title":"Exon-Skipping in Duchenne Muscular Dystrophy","volume":"8","author":"Takeda","year":"2021","journal-title":"J.\u00a0Neuromuscul. Dis."},{"key":"10.1016\/j.omtn.2024.102401_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0178700","article-title":"Frameshift indels introduced by genome editing can lead to in-frame exon skipping","volume":"12","author":"Lalonde","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.omtn.2024.102401_bib40","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/978-1-61779-767-5_15","article-title":"Antisense-mediated exon skipping to reframe transcripts","volume":"867","author":"Turczynski","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.omtn.2024.102401_bib41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.gde.2020.02.017","article-title":"DNA polymerase theta (Pol\u03b8) - an error-prone polymerase necessary for genome stability","volume":"60","author":"Brambati","year":"2020","journal-title":"Curr. Opin. Genet. Dev."},{"key":"10.1016\/j.omtn.2024.102401_bib42","article-title":"Transcriptomic assessing and guiding DSB repair pathway activity towards precise genomic engineering of post-mitotic neurons","volume":"60","author":"Pasquini","year":"2019","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.omtn.2024.102401_bib43","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1093\/hmg\/7.5.831","article-title":"Retrovirus-mediated enzymatic correction of Tay-Sachs defect in transduced and non-transduced cells","volume":"7","author":"Guidotti","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtn.2024.102401_bib44","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-replace genome editing without double-strand breaks or donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.omtn.2024.102401_bib45","doi-asserted-by":"crossref","first-page":"W171","DOI":"10.1093\/nar\/gkz365","article-title":"CHOPCHOP v3: Expanding the CRISPR web toolbox beyond genome editing","volume":"47","author":"Labun","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2024.102401_bib46","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1038\/nprot.2016.141","article-title":"A high-throughput functional genomics workflow based on CRISPR\/Cas9-mediated targeted mutagenesis in zebrafish","volume":"11","author":"Varshney","year":"2016","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.omtn.2024.102401_bib47","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1038\/s41596-022-00724-4","article-title":"Designing and executing prime editing experiments in mammalian cells","volume":"17","author":"Doman","year":"2022","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.omtn.2024.102401_bib48","doi-asserted-by":"crossref","first-page":"W499","DOI":"10.1093\/nar\/gkab319","article-title":"PE-Designer and PE-analyzer: Web-based design and analysis tools for CRISPR prime editing","volume":"49","author":"Hwang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2024.102401_bib49","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41587-021-01039-7","article-title":"Engineered pegRNAs improve prime editing efficiency","volume":"40","author":"Nelson","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2024.102401_bib50","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1089\/crispr.2021.0113","article-title":"Inference of CRISPR Edits from Sanger Trace Data","volume":"5","author":"Conant","year":"2022","journal-title":"Cris. J."},{"key":"10.1016\/j.omtn.2024.102401_bib51","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1083\/jcb.100.3.965","article-title":"Nile red: A selective fluorescent stain for intracellular lipid droplets","volume":"100","author":"Greenspan","year":"1985","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.omtn.2024.102401_bib52","doi-asserted-by":"crossref","first-page":"W431","DOI":"10.1093\/nar\/gkab314","article-title":"Mol\u2217 Viewer: modern web app for 3D visualization and analysis of large biomolecular structures","volume":"49","author":"Sehnal","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["Molecular Therapy Nucleic Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253124002889?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253124002889?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T11:28:10Z","timestamp":1762601290000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2162253124002889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["S2162253124002889"],"URL":"https:\/\/doi.org\/10.1016\/j.omtn.2024.102401","relation":{},"ISSN":["2162-2531"],"issn-type":[{"value":"2162-2531","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Nucleic Acids","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtn.2024.102401","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}],"article-number":"102401"}}