{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T22:03:08Z","timestamp":1772229788563,"version":"3.50.1"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1086311"],"award-info":[{"award-number":["1086311"]}],"id":[{"id":"10.13039\/501100000925","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":[[2018,6]]},"DOI":"10.1016\/j.omtn.2018.01.011","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T08:09:08Z","timestamp":1517386148000},"page":"91-102","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Antisense Oligonucleotide-Mediated Terminal Intron Retention of the SMN2 Transcript"],"prefix":"10.1016","volume":"11","author":[{"given":"Loren L.","family":"Flynn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chalermchai","family":"Mitrpant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ianthe L.","family":"Pitout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve D.","family":"Wilton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtn.2018.01.011_bib1","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1086\/515465","article-title":"Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number","volume":"60","author":"McAndrew","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtn.2018.01.011_bib2","first-page":"15","article-title":"Spinal muscular atrophy: a motor neuron disorder or a multi-organ disease?","volume":"224","author":"Shababi","year":"2014","journal-title":"J.\u00a0Anat."},{"key":"10.1016\/j.omtn.2018.01.011_bib3","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtn.2018.01.011_bib4","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","article-title":"A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2","volume":"8","author":"Monani","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtn.2018.01.011_bib5","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1089\/hum.2012.225","article-title":"Antisense oligonucleotides for the treatment of spinal muscular atrophy","volume":"24","author":"Porensky","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtn.2018.01.011_bib6","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.2018.01.011_bib7","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1016\/S0140-6736(16)31408-8","article-title":"Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study","volume":"388","author":"Finkel","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.omtn.2018.01.011_bib8","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1128\/MCB.26.4.1333-1346.2006","article-title":"Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron","volume":"26","author":"Singh","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.omtn.2018.01.011_bib9","unstructured":"U.S. Food and Drug Administration. (2016). FDA approves first drug for spinal\u00a0muscular atrophy. December 23, 2016. https:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm534611.htm."},{"key":"10.1016\/j.omtn.2018.01.011_bib10","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1093\/hmg\/ddu198","article-title":"Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models","volume":"23","author":"Osman","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtn.2018.01.011_bib11","doi-asserted-by":"crossref","first-page":"8144","DOI":"10.1093\/nar\/gkt609","article-title":"An intronic structure enabled by a long-distance interaction serves as a novel target for splicing correction in spinal muscular atrophy","volume":"41","author":"Singh","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2018.01.011_bib12","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.ajhg.2008.01.014","article-title":"Antisense masking of an hnRNP A1\/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice","volume":"82","author":"Hua","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtn.2018.01.011_bib13","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1101\/gad.252106.114","article-title":"Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate","volume":"28","author":"Fong","year":"2014","journal-title":"Genes Dev."},{"key":"10.1016\/j.omtn.2018.01.011_bib14","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.molcel.2014.03.044","article-title":"How slow RNA polymerase II elongation favors alternative exon skipping","volume":"54","author":"Dujardin","year":"2014","journal-title":"Mol. Cell"},{"key":"10.1016\/j.omtn.2018.01.011_bib15","doi-asserted-by":"crossref","first-page":"45476","DOI":"10.1074\/jbc.M107632200","article-title":"Modulation of survival motor neuron pre-mRNA splicing by inhibition of alternative 3\u2032 splice site pairing","volume":"276","author":"Lim","year":"2001","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.omtn.2018.01.011_bib16","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1007\/s00018-012-0990-9","article-title":"Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements","volume":"69","author":"Barrett","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.omtn.2018.01.011_bib17","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1101\/gr.177790.114","article-title":"Widespread intron retention in mammals functionally tunes transcriptomes","volume":"24","author":"Braunschweig","year":"2014","journal-title":"Genome Res."},{"key":"10.1016\/j.omtn.2018.01.011_bib18","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/bies.201200073","article-title":"Introns in UTRs: why we should stop ignoring them","volume":"34","author":"Bicknell","year":"2012","journal-title":"BioEssays"},{"key":"10.1016\/j.omtn.2018.01.011_bib19","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nature06495","article-title":"Translational control of intron splicing in eukaryotes","volume":"451","author":"Jaillon","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.omtn.2018.01.011_bib20","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/bies.201300156","article-title":"The functional consequences of intron retention: alternative splicing coupled to NMD as a regulator of gene expression","volume":"36","author":"Ge","year":"2014","journal-title":"BioEssays"},{"key":"10.1016\/j.omtn.2018.01.011_bib21","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1101\/gad.188037.112","article-title":"Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention","volume":"26","author":"Yap","year":"2012","journal-title":"Genes Dev."},{"key":"10.1016\/j.omtn.2018.01.011_bib22","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.cell.2013.06.052","article-title":"Orchestrated intron retention regulates normal granulocyte differentiation","volume":"154","author":"Wong","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.omtn.2018.01.011_bib23","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1101\/gad.1525507","article-title":"Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay","volume":"21","author":"Ni","year":"2007","journal-title":"Genes Dev."},{"key":"10.1016\/j.omtn.2018.01.011_bib24","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1128\/MCB.00070-15","article-title":"Regulated intron retention and nuclear pre-mRNA decay contribute to PABPN1 autoregulation","volume":"35","author":"Bergeron","year":"2015","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.omtn.2018.01.011_bib25","doi-asserted-by":"crossref","first-page":"15134","DOI":"10.1038\/ncomms15134","article-title":"Intron retention is regulated by altered MeCP2-mediated splicing factor recruitment","volume":"8","author":"Wong","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.omtn.2018.01.011_bib26","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1093\/nar\/gkp215","article-title":"Human Splicing Finder: an online bioinformatics tool to predict splicing signals","volume":"37","author":"Desmet","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2018.01.011_bib27","doi-asserted-by":"crossref","first-page":"D75","DOI":"10.1093\/nar\/gkp902","article-title":"UTRdb and UTRsite (RELEASE 2010): a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs","volume":"38","author":"Grillo","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2018.01.011_bib28","doi-asserted-by":"crossref","first-page":"D68","DOI":"10.1093\/nar\/gkt1181","article-title":"miRBase: annotating high confidence microRNAs using deep sequencing data","volume":"42","author":"Kozomara","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtn.2018.01.011_bib29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0378-1119(99)00104-3","article-title":"Detection of polyadenylation signals in human DNA sequences","volume":"231","author":"Tabaska","year":"1999","journal-title":"Gene"},{"key":"10.1016\/j.omtn.2018.01.011_bib30","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/bioinformatics\/bth437","article-title":"DNAFSMiner: a web-based software toolbox to recognize two types of functional sites in DNA sequences","volume":"21","author":"Liu","year":"2005","journal-title":"Bioinformatics"},{"key":"10.1016\/j.omtn.2018.01.011_bib31","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.1242\/dev.124.23.4847","article-title":"The Bearded box, a novel 3\u2032 UTR sequence motif, mediates negative post-transcriptional regulation of Bearded and Enhancer of split Complex gene expression","volume":"124","author":"Lai","year":"1997","journal-title":"Development"},{"key":"10.1016\/j.omtn.2018.01.011_bib32","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1242\/dev.125.20.4077","article-title":"The K box, a conserved 3\u2032 UTR sequence motif, negatively regulates accumulation of enhancer of split complex transcripts","volume":"125","author":"Lai","year":"1998","journal-title":"Development"},{"key":"10.1016\/j.omtn.2018.01.011_bib33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1471-2199-8-57","article-title":"Antisense oligonucleotide induced exon skipping and the dystrophin gene transcript: cocktails and chemistries","volume":"8","author":"Adams","year":"2007","journal-title":"BMC Mol. Biol."},{"key":"10.1016\/j.omtn.2018.01.011_bib34","doi-asserted-by":"crossref","first-page":"e62114","DOI":"10.1371\/journal.pone.0062114","article-title":"Improved antisense oligonucleotide design to suppress aberrant SMN2 gene transcript processing: towards a treatment for spinal muscular atrophy","volume":"8","author":"Mitrpant","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtn.2018.01.011_bib35","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.24555","article-title":"Longitudinal effect of eteplirsen vs. historical control on ambulation in DMD","volume":"79","author":"Mendell","year":"2016","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.omtn.2018.01.011_bib36","unstructured":"U.S. Food and Drug Administration. (2016). FDA News Release: FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. September 19, 2016. http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm521263.htm."},{"issue":"Suppl 1","key":"10.1016\/j.omtn.2018.01.011_bib37","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1016\/S0960-8966(02)00086-X","article-title":"Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy","volume":"12","author":"Aartsma-Rus","year":"2002","journal-title":"Neuromuscul. Disord."},{"key":"10.1016\/j.omtn.2018.01.011_bib38","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00439-006-0218-x","article-title":"A systematic analysis of disease-associated variants in the 3\u2032 regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3\u2032 UTR variants","volume":"120","author":"Chen","year":"2006","journal-title":"Hum. Genet."},{"key":"10.1016\/j.omtn.2018.01.011_bib39","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1002\/ijc.29324","article-title":"Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity","volume":"136","author":"Madhavan","year":"2015","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.omtn.2018.01.011_bib40","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/ng865","article-title":"Micro RNAs are complementary to 3\u2032 UTR sequence motifs that mediate negative post-transcriptional regulation","volume":"30","author":"Lai","year":"2002","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtn.2018.01.011_bib41","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s10637-016-0407-y","article-title":"Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors","volume":"35","author":"Beg","year":"2017","journal-title":"Invest New Drugs"},{"key":"10.1016\/j.omtn.2018.01.011_bib42","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1101\/gr.10.7.1001","article-title":"Patterns of variant polyadenylation signal usage in human genes","volume":"10","author":"Beaudoing","year":"2000","journal-title":"Genome Res."},{"key":"10.1016\/j.omtn.2018.01.011_bib43","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1074\/jbc.M113.538264","article-title":"U1A regulates 3\u2032 processing of the survival motor neuron mRNA","volume":"289","author":"Workman","year":"2014","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.omtn.2018.01.011_bib44","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1093\/molbev\/msl111","article-title":"Intron size, abundance, and distribution within untranslated regions of genes","volume":"23","author":"Hong","year":"2006","journal-title":"Mol. Biol. Evol."},{"key":"10.1016\/j.omtn.2018.01.011_bib45","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/humu.21609","article-title":"SpliceAid 2: a database of human splicing factors expression data and RNA target motifs","volume":"33","author":"Piva","year":"2012","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.omtn.2018.01.011_bib46","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/jgm.295","article-title":"Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophy","volume":"4","author":"Mann","year":"2002","journal-title":"J.\u00a0Gene Med."}],"container-title":["Molecular Therapy Nucleic Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S216225311830012X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S216225311830012X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:13:22Z","timestamp":1772226802000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S216225311830012X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":46,"alternative-id":["S216225311830012X"],"URL":"https:\/\/doi.org\/10.1016\/j.omtn.2018.01.011","relation":{},"ISSN":["2162-2531"],"issn-type":[{"value":"2162-2531","type":"print"}],"subject":[],"published":{"date-parts":[[2018,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Antisense Oligonucleotide-Mediated Terminal Intron Retention of the SMN2 Transcript","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Nucleic Acids","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtn.2018.01.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The Authors.","name":"copyright","label":"Copyright"}]}}