{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:52:05Z","timestamp":1793069525736,"version":"4.5.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T00:00:00Z","timestamp":1563321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","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":[[2019,9]]},"DOI":"10.1016\/j.omtn.2019.07.004","type":"journal-article","created":{"date-parts":[[2019,7,20]],"date-time":"2019-07-20T00:01:46Z","timestamp":1563580906000},"page":"601-614","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":56,"special_numbering":"C","title":["Suppression of Mutant Protein Expression in SCA3 and SCA1 Mice Using a CAG Repeat-Targeting Antisense Oligonucleotide"],"prefix":"10.1016","volume":"17","author":[{"given":"Eleni","family":"Kourkouta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudie","family":"Weij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchel","family":"Gonz\u00e1lez-Barriga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Mulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruurd","family":"Verheul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sieto","family":"Bosgra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas","family":"Groenendaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Puoliv\u00e4li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Toivanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith C.T.","family":"van Deutekom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Datson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtn.2019.07.004_bib1","series-title":"GeneReviews","first-page":"1993","article-title":"Hereditary Ataxia Overview","author":"Bird","year":"1993"},{"key":"10.1016\/j.omtn.2019.07.004_bib2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrn.2017.92","article-title":"Polyglutamine spinocerebellar ataxias\u2014from genes to potential treatments","volume":"18","author":"Paulson","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.omtn.2019.07.004_bib3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/acn3.156","article-title":"Survival and severity in dominant cerebellar ataxias","volume":"2","author":"Monin","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.omtn.2019.07.004_bib4","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s10072-016-2594-x","article-title":"High relative frequency of SCA1 in Poland reflecting a potential founder effect","volume":"37","author":"Krysa","year":"2016","journal-title":"Neurol. Sci."},{"key":"10.1016\/j.omtn.2019.07.004_bib5","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1212\/WNL.58.5.702","article-title":"Spinocerebellar ataxias in the Netherlands: prevalence and age at onset variance analysis","volume":"58","author":"van de Warrenburg","year":"2002","journal-title":"Neurology"},{"key":"10.1016\/j.omtn.2019.07.004_bib6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/ejhg.2009.215","article-title":"The (CAG)n tract of Machado-Joseph Disease gene (ATXN3): a comparison between DNA and mRNA in patients and controls","volume":"18","author":"Bettencourt","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.omtn.2019.07.004_bib7","doi-asserted-by":"crossref","first-page":"e1003648","DOI":"10.1371\/journal.pgen.1003648","article-title":"The role of interruptions in polyQ in the pathology of SCA1","volume":"9","author":"Menon","year":"2013","journal-title":"PLoS Genet."},{"key":"10.1016\/j.omtn.2019.07.004_bib8","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","article-title":"Trinucleotide repeat disorders","volume":"30","author":"Orr","year":"2007","journal-title":"Annu. Rev. Neurosci."},{"key":"10.1016\/j.omtn.2019.07.004_bib9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/B978-0-444-51892-7.00005-X","article-title":"Neuropathology of degenerative ataxias","volume":"103","author":"Fratkin","year":"2012","journal-title":"Handb. Clin. Neurol."},{"key":"10.1016\/j.omtn.2019.07.004_bib10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s13311-018-00696-y","article-title":"Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias","volume":"16","author":"Buijsen","year":"2019","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.omtn.2019.07.004_bib11","first-page":"347","article-title":"Antisense oligonucleotides: basic concepts and mechanisms","volume":"1","author":"Dias","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.omtn.2019.07.004_bib12","article-title":"Antisense oligonucleotides in neurological disorders","volume":"11","author":"Wurster","year":"2018","journal-title":"Ther. Adv. Neurol. Disorder."},{"key":"10.1016\/j.omtn.2019.07.004_bib13","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1212\/WNL.0000000000002445","article-title":"Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy","volume":"86","author":"Chiriboga","year":"2016","journal-title":"Neurology"},{"key":"10.1016\/j.omtn.2019.07.004_bib14","unstructured":"US Food and Drug Administration. (2016). FDA News Release: FDA approves first drug for spinal muscular atrophy, December 23, 2016. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-drug-spinal-muscular-atrophy."},{"key":"10.1016\/j.omtn.2019.07.004_bib15","unstructured":"Ionis Pharmaceuticals, Inc. (2018). Press Release: new data from IONIS-HTT Rx phase 1\/2 study demonstrates correlation between reduction of disease-causing protein and improvement in clinical measures of Huntington\u2019s disease, April 24, 2018. https:\/\/ir.ionispharma.com\/news-releases\/news-release-details\/new-data-ionis-htt-rx-phase-12-study-demonstrates-correlation."},{"key":"10.1016\/j.omtn.2019.07.004_bib16","doi-asserted-by":"crossref","first-page":"e0171127","DOI":"10.1371\/journal.pone.0171127","article-title":"The expanded CAG repeat in the huntingtin gene as target for therapeutic RNA modulation throughout the HD mouse brain","volume":"12","author":"Datson","year":"2017","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtn.2019.07.004_bib17","doi-asserted-by":"crossref","first-page":"e24308","DOI":"10.1371\/journal.pone.0024308","article-title":"Targeting several CAG expansion diseases by a single antisense oligonucleotide","volume":"6","author":"Evers","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtn.2019.07.004_bib18","doi-asserted-by":"crossref","first-page":"9570","DOI":"10.1093\/nar\/gkt693","article-title":"ss-siRNAs allele selectively inhibit ataxin-3 expression: multiple mechanisms for an alternative gene silencing strategy","volume":"41","author":"Liu","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2019.07.004_bib19","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.omtn.2017.06.019","article-title":"Antisense Oligonucleotide-Mediated Removal of the Polyglutamine Repeat in Spinocerebellar Ataxia Type 3 Mice","volume":"8","author":"Toonen","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.omtn.2019.07.004_bib20","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1093\/hmg\/11.9.1075","article-title":"YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a mild and slowly progressive cerebellar deficit","volume":"11","author":"Cemal","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtn.2019.07.004_bib21","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1038\/mt.2013.144","article-title":"Toward RNAi therapy for the polyglutamine disease Machado-Joseph disease","volume":"21","author":"Costa","year":"2013","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtn.2019.07.004_bib22","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0896-6273(02)00733-X","article-title":"A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration","volume":"34","author":"Watase","year":"2002","journal-title":"Neuron"},{"key":"10.1016\/j.omtn.2019.07.004_bib23","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/378403a0","article-title":"Polyglutamine expansion as a pathological epitope in Huntington\u2019s disease and four dominant cerebellar ataxias","volume":"378","author":"Trottier","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.omtn.2019.07.004_bib24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/ng0595-94","article-title":"Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals","volume":"10","author":"Servadio","year":"1995","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtn.2019.07.004_bib25","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.neuron.2019.01.039","article-title":"Huntingtin Lowering Strategies for Disease Modification in Huntington\u2019s Disease","volume":"101","author":"Tabrizi","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.omtn.2019.07.004_bib26","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.1172\/JCI83185","article-title":"Targeting CAG repeat RNAs reduces Huntington\u2019s disease phenotype independently of huntingtin levels","volume":"126","author":"Ru\u00e9","year":"2016","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.omtn.2019.07.004_bib27","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1021\/bi101208k","article-title":"Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat","volume":"49","author":"Gagnon","year":"2010","journal-title":"Biochemistry"},{"key":"10.1016\/j.omtn.2019.07.004_bib28","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/nbt.1539","article-title":"Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs","volume":"27","author":"Hu","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtn.2019.07.004_bib29","doi-asserted-by":"crossref","first-page":"5578","DOI":"10.1093\/nar\/gkr156","article-title":"Inhibition of mutant huntingtin expression by RNA duplex targeting expanded CAG repeats","volume":"39","author":"Fiszer","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2019.07.004_bib30","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/hmg\/11.2.175","article-title":"Rescue of polyglutamine-mediated cytotoxicity by double-stranded RNA-mediated RNA interference","volume":"11","author":"Caplen","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtn.2019.07.004_bib31","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/ana.24656","article-title":"DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases","volume":"79","author":"Bettencourt","year":"2016","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.omtn.2019.07.004_bib32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/nat.2017.0682","article-title":"Development of Exon Skipping Therapies for Duchenne Muscular Dystrophy: A Critical Review and a Perspective on the Outstanding Issues","volume":"27","author":"Aartsma-Rus","year":"2017","journal-title":"Nucleic Acid Ther."},{"key":"10.1016\/j.omtn.2019.07.004_bib33","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1073\/pnas.1221891110","article-title":"Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease","volume":"110","author":"Sathasivam","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtn.2019.07.004_bib34","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1128\/MCB.23.13.4485-4493.2003","article-title":"Selectable system for monitoring the instability of CTG\/CAG triplet repeats in mammalian cells","volume":"23","author":"Gorbunova","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.omtn.2019.07.004_bib35","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/0092-8674(93)90316-I","article-title":"Specific interactions between proteins implicated in splice site selection and regulated alternative splicing","volume":"75","author":"Wu","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2019.07.004_bib36","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/oli.2005.15.284","article-title":"Functional analysis of 114 exon-internal AONs for targeted DMD exon skipping: indication for steric hindrance of SR protein binding sites","volume":"15","author":"Aartsma-Rus","year":"2005","journal-title":"Oligonucleotides"},{"key":"10.1016\/j.omtn.2019.07.004_bib37","doi-asserted-by":"crossref","first-page":"12700","DOI":"10.1073\/pnas.0506344102","article-title":"Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain","volume":"102","author":"Mao","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtn.2019.07.004_bib38","doi-asserted-by":"crossref","first-page":"e13695","DOI":"10.1371\/journal.pone.0013695","article-title":"Splice isoforms of the polyglutamine disease protein ataxin-3 exhibit similar enzymatic yet different aggregation properties","volume":"5","author":"Harris","year":"2010","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtn.2019.07.004_bib39","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1126\/science.1279811","article-title":"Antisense and antigene properties of peptide nucleic acids","volume":"258","author":"Hanvey","year":"1992","journal-title":"Science"},{"key":"10.1016\/j.omtn.2019.07.004_bib40","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/502","article-title":"Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1","volume":"19","author":"Cummings","year":"1998","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtn.2019.07.004_bib41","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0092-8674(00)81781-X","article-title":"Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice","volume":"95","author":"Klement","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2019.07.004_bib42","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2990.2006.00819.x","article-title":"Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress","volume":"33","author":"Woulfe","year":"2007","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"10.1016\/j.omtn.2019.07.004_bib43","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.123193","article-title":"Antisense oligonucleotide-mediated ataxin-1 reduction prolongs survival in SCA1 mice and reveals disease-associated transcriptome profiles","volume":"3","author":"Friedrich","year":"2018","journal-title":"JCI Insight"},{"key":"10.1016\/j.omtn.2019.07.004_bib44","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nature12204","article-title":"RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1","volume":"498","author":"Park","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.omtn.2019.07.004_bib45","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1073\/pnas.1018748108","article-title":"Regional rescue of spinocerebellar ataxia type 1 phenotypes by 14-3-3epsilon haploinsufficiency in mice underscores complex pathogenicity in neurodegeneration","volume":"108","author":"Jafar-Nejad","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtn.2019.07.004_bib46","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s12017-010-8137-3","article-title":"Mouse ataxin-3 functional knock-out model","volume":"13","author":"Switonski","year":"2011","journal-title":"Neuromolecular Med."},{"key":"10.1016\/j.omtn.2019.07.004_bib47","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtn.2019.07.004_bib48","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtn.2019.07.004_bib49","doi-asserted-by":"crossref","first-page":"e0162467","DOI":"10.1371\/journal.pone.0162467","article-title":"Digital Droplet PCR for the Absolute Quantification of Exon Skipping Induced by Antisense Oligonucleotides in (Pre-)Clinical Development for Duchenne Muscular Dystrophy","volume":"11","author":"Verheul","year":"2016","journal-title":"PLoS ONE"}],"container-title":["Molecular Therapy - Nucleic Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253119301945?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253119301945?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T15:38:19Z","timestamp":1717688299000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2162253119301945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9]]},"references-count":49,"alternative-id":["S2162253119301945"],"URL":"https:\/\/doi.org\/10.1016\/j.omtn.2019.07.004","relation":{},"ISSN":["2162-2531"],"issn-type":[{"value":"2162-2531","type":"print"}],"subject":[],"published":{"date-parts":[[2019,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Suppression of Mutant Protein Expression in SCA3 and SCA1 Mice Using a CAG Repeat-Targeting Antisense Oligonucleotide","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Nucleic Acids","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtn.2019.07.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Author(s).","name":"copyright","label":"Copyright"}]}}