{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:44:28Z","timestamp":1770741868087,"version":"3.49.0"},"reference-count":97,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001157","name":"Harvard NeuroDiscovery Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001157","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS105709"],"award-info":[{"award-number":["NS105709"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS119471"],"award-info":[{"award-number":["NS119471"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Methods &amp; Clinical Development"],"published-print":{"date-parts":[[2022,6]]},"DOI":"10.1016\/j.omtm.2022.03.001","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T04:57:52Z","timestamp":1646369872000},"page":"84-95","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington's disease"],"prefix":"10.1016","volume":"25","author":[{"given":"Jun Wan","family":"Shin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aram","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seri S.","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-0787","authenticated-orcid":false,"given":"Jong-Min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2022.03.001_bib1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. the Huntington's Disease Collaborative Research Group","volume":"72","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ajhg.2015.12.018","article-title":"The HTT CAG-expansion mutation determines age at death but not disease duration in huntington disease","volume":"98","author":"Keum","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib3","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nrg1686","article-title":"History of genetic disease: the molecular genetics of Huntington disease - a history","volume":"6","author":"Bates","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.omtm.2022.03.001_bib5","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/ng0893-398","article-title":"The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease","volume":"4","author":"Andrew","year":"1993","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib6","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/ng0893-387","article-title":"Trinucleotide repeat length instability and age of onset in Huntington's disease","volume":"4","author":"Duyao","year":"1993","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib7","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1212\/WNL.0b013e318249f683","article-title":"CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion","volume":"78","author":"Lee","year":"2012","journal-title":"Neurology"},{"key":"10.1016\/j.omtm.2022.03.001_bib8","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1002\/mds.26006","article-title":"Animal models of Huntington's disease for translation to the clinic: best practices","volume":"29","author":"Menalled","year":"2014","journal-title":"Move. Disord."},{"key":"10.1016\/j.omtm.2022.03.001_bib9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nrn1806","article-title":"Normal huntingtin function: an alternative approach to Huntington's disease","volume":"6","author":"Cattaneo","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.omtm.2022.03.001_bib10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3233\/JHD-130072","article-title":"Surveying the landscape of Huntington's disease mechanisms, measurements, and medicines","volume":"2","author":"Crook","year":"2013","journal-title":"J.\u00a0Huntington's Dis."},{"key":"10.1016\/j.omtm.2022.03.001_bib11","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/hmg\/ddl013","article-title":"Regional and cellular gene expression changes in human Huntington's disease brain","volume":"15","author":"Hodges","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0168-9525(03)00074-X","article-title":"Transcriptional abnormalities in Huntington disease","volume":"19","author":"Sugars","year":"2003","journal-title":"Trends Genetics"},{"key":"10.1016\/j.omtm.2022.03.001_bib13","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1126\/science.1056784","article-title":"Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity","volume":"291","author":"Nucifora","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.omtm.2022.03.001_bib14","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0166-2236(00)01609-X","article-title":"Transcriptional dysregulation in Huntington's disease","volume":"23","author":"Cha","year":"2000","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.omtm.2022.03.001_bib15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1126\/science.1059581","article-title":"Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease","volume":"293","author":"Zuccato","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.omtm.2022.03.001_bib16","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nm0309-253","article-title":"Getting a handle on Huntington's disease: the case for cholesterol","volume":"15","author":"Katsuno","year":"2009","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2022.03.001_bib17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.cell.2006.10.023","article-title":"PGC-1alpha, a new therapeutic target in Huntington's disease?","volume":"127","author":"McGill","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib18","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1093\/hmg\/ddi319","article-title":"HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism","volume":"14","author":"Seong","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1056\/NEJM198702123160701","article-title":"Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease","volume":"316","author":"Mazziotta","year":"1987","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtm.2022.03.001_bib20","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/ana.410200305","article-title":"PET scan investigations of Huntington's disease: cerebral metabolic correlates of neurological features and functional decline","volume":"20","author":"Young","year":"1986","journal-title":"Ann. Neurol."},{"issue":"Suppl","key":"10.1016\/j.omtm.2022.03.001_bib21","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1038\/nm1066","article-title":"Protein aggregation and neurodegenerative disease","volume":"10","author":"Ross","year":"2004","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2022.03.001_bib22","doi-asserted-by":"crossref","first-page":"11404","DOI":"10.1073\/pnas.96.20.11404","article-title":"Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells","volume":"96","author":"Kazantsev","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.omtm.2022.03.001_bib23","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0092-8674(00)80514-0","article-title":"Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in\u00a0vitro and in\u00a0vivo","volume":"90","author":"Scherzinger","year":"1997","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib24","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1046\/j.1471-4159.2001.00689.x","article-title":"Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease","volume":"79","author":"Bogdanov","year":"2001","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.omtm.2022.03.001_bib25","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.neuroscience.2012.05.043","article-title":"Dysregulation of synaptic proteins, dendritic spine abnormalities and pathological plasticity of synapses as experience-dependent mediators of cognitive and psychiatric symptoms in Huntington's disease","volume":"251","author":"Nithianantharajah","year":"2013","journal-title":"Neuroscience"},{"key":"10.1016\/j.omtm.2022.03.001_bib26","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.cell.2004.06.022","article-title":"Huntington's disease: new paths to pathogenesis","volume":"118","author":"Ross","year":"2004","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib27","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41582-020-0389-4","article-title":"Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities","volume":"16","author":"Tabrizi","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.omtm.2022.03.001_bib28","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S1474-4422(17)30280-6","article-title":"Therapies targeting DNA and RNA in Huntington's disease","volume":"16","author":"Wild","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.omtm.2022.03.001_bib29","doi-asserted-by":"crossref","first-page":"R53","DOI":"10.1093\/hmg\/ddv442","article-title":"Gene suppression strategies for dominantly inherited neurodegenerative diseases: lessons from Huntington's disease and spinocerebellar ataxia","volume":"25","author":"Keiser","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib30","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1002\/mds.26020","article-title":"Huntingtin-lowering strategies in Huntington's disease: antisense oligonucleotides, small RNAs, and gene editing","volume":"29","author":"Aronin","year":"2014","journal-title":"Move. Disord."},{"key":"10.1016\/j.omtm.2022.03.001_bib31","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1056\/NEJMoa1900907","article-title":"Targeting huntingtin expression in patients with Huntington's disease","volume":"380","author":"Tabrizi","year":"2019","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtm.2022.03.001_bib32","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1136\/jnnp.2007.128728","article-title":"Detection of Huntington's disease decades before diagnosis: the Predict-HD study","volume":"79","author":"Paulsen","year":"2008","journal-title":"J.\u00a0Neurol. Neurosurg. Psychiatr."},{"key":"10.1016\/j.omtm.2022.03.001_bib33","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/0092-8674(95)90542-1","article-title":"Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes","volume":"81","author":"Nasir","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib34","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/ng1297-404","article-title":"Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion","volume":"17","author":"White","year":"1997","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/ng1095-155","article-title":"Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue","volume":"11","author":"Zeitlin","year":"1995","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib36","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/ejhg.2016.74","article-title":"A novel neurodevelopmental disorder associated with compound heterozygous variants in the huntingtin gene","volume":"24","author":"Rodan","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib37","doi-asserted-by":"crossref","first-page":"e1006846","DOI":"10.1371\/journal.pgen.1006846","article-title":"Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits, bilateral thalamic calcification, and altered brain iron homeostasis","volume":"13","author":"Dietrich","year":"2017","journal-title":"PLoS Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib38","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1073\/pnas.1524575113","article-title":"Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis","volume":"113","author":"Wang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.omtm.2022.03.001_bib39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/BF02257483","article-title":"Structure and expression of the Huntington's disease gene: evidence against simple inactivation due to an expanded CAG repeat","volume":"20","author":"Ambrose","year":"1994","journal-title":"Somatic Cell Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib40","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.expneurol.2009.03.004","article-title":"A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference","volume":"217","author":"Lombardi","year":"2009","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.omtm.2022.03.001_bib41","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cub.2009.03.030","article-title":"Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients","volume":"19","author":"Pfister","year":"2009","journal-title":"Curr. Biol."},{"key":"10.1016\/j.omtm.2022.03.001_bib42","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.ajhg.2019.10.011","article-title":"A comprehensive haplotype-targeting strategy for allele-specific HTT suppression in huntington disease","volume":"105","author":"Kay","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib43","doi-asserted-by":"crossref","first-page":"e107434","DOI":"10.1371\/journal.pone.0107434","article-title":"Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: providing a therapeutic option for all Huntington disease patients","volume":"9","author":"Skotte","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2022.03.001_bib44","doi-asserted-by":"crossref","first-page":"9634","DOI":"10.1093\/nar\/gkt725","article-title":"Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS","volume":"41","author":"Ostergaard","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2022.03.001_bib45","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1038\/mt.2011.201","article-title":"Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene\/allele-specific silencing of mutant huntingtin","volume":"19","author":"Carroll","year":"2011","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2022.03.001_bib46","doi-asserted-by":"crossref","first-page":"eaar3959","DOI":"10.1126\/scitranslmed.aar3959","article-title":"Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease","volume":"10","author":"Southwell","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.omtm.2022.03.001_bib47","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1038\/mt.2014.153","article-title":"In\u00a0vivo evaluation of candidate allele-specific mutant huntingtin gene silencing antisense oligonucleotides","volume":"22","author":"Southwell","year":"2014","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2022.03.001_bib48","first-page":"4566","article-title":"Permanent inactivation of Huntington's disease mutation by personalized allele-specific CRISPR\/Cas9","volume":"25","author":"Shin","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ymthe.2016.11.010","article-title":"CRISPR\/Cas9 editing of the mutant huntingtin allele in\u00a0vitro and in\u00a0vivo","volume":"25","author":"Monteys","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2022.03.001_bib50","doi-asserted-by":"crossref","first-page":"e2248","DOI":"10.1371\/journal.pone.0002248","article-title":"Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi","volume":"3","author":"Ohnishi","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2022.03.001_bib51","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41587-021-00955-y","article-title":"Questions swirl around failures of disease-modifying Huntington's drugs","volume":"39","author":"Sheridan","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2022.03.001_bib52","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.ajhg.2012.01.005","article-title":"Common SNP-based haplotype analysis of the 4p16.3 Huntington disease gene region","volume":"90","author":"Lee","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib53","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.ajhg.2015.07.017","article-title":"Sequence-level analysis of the major European huntington disease haplotype","volume":"97","author":"Lee","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib54","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.cell.2015.07.003","article-title":"Identification of genetic factors that modify clinical onset of Huntington's disease","volume":"162","author":"GeM-HD Consortium","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib55","article-title":"Huntington's disease onset is determined by length of uninterrupted CAG, not encoded polyglutamine, and is modified by DNA maintenance mechanisms","author":"GeM-HD Consortium","year":"2019","journal-title":"bioRxiv"},{"key":"10.1016\/j.omtm.2022.03.001_bib56","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/ejhg.2017.125","article-title":"Haplotype-based stratification of Huntington's disease","volume":"25","author":"Chao","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib57","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1038\/mt.2015.128","article-title":"Huntingtin haplotypes provide prioritized target panels for allele-specific silencing in huntington disease patients of European ancestry","volume":"23","author":"Kay","year":"2015","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2022.03.001_bib58","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1471-4159.2008.05734.x","article-title":"Allele-specific silencing of mutant Huntington's disease gene","volume":"108","author":"Zhang","year":"2009","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.omtm.2022.03.001_bib59","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1093\/hmg\/ddx033","article-title":"Novel allele-specific quantification methods reveal no effects of adult onset CAG repeats on HTT mRNA and protein levels","volume":"26","author":"Shin","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib60","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)80623-6","article-title":"Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease","volume":"101","author":"Yamamoto","year":"2000","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib61","series-title":"Roche Provides Update on Tominersen Programme in Manifest Huntington\u2019s Disease","author":"Relations","year":"2021"},{"key":"10.1016\/j.omtm.2022.03.001_bib62","series-title":"Huntington\u2019s Disease: 2 Steps Backward, 1 Step Forward","author":"Lewis","year":"2021"},{"key":"10.1016\/j.omtm.2022.03.001_bib63","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1073\/pnas.1919197117","article-title":"Lack of RAN-mediated toxicity in Huntington's disease knock-in mice","volume":"117","author":"Yang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.omtm.2022.03.001_bib64","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1038\/s41598-017-01510-z","article-title":"The pathogenic exon 1 HTT protein is produced by incomplete splicing in Huntington's disease patients","volume":"7","author":"Neueder","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2022.03.001_bib65","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.neuron.2015.10.038","article-title":"RAN translation in huntington disease","volume":"88","author":"Banez-Coronel","year":"2015","journal-title":"Neuron"},{"key":"10.1016\/j.omtm.2022.03.001_bib66","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. U S A"},{"key":"10.1016\/j.omtm.2022.03.001_bib67","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1093\/brain\/awab190","article-title":"Huntingtin silencing delays onset and slows progression of Huntington's disease: a biomarker study","volume":"144","author":"Liu","year":"2021","journal-title":"Brain"},{"key":"10.1016\/j.omtm.2022.03.001_bib68","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/ng0595-3","article-title":"Gain of glutamines, gain of function?","volume":"10","author":"Housman","year":"1995","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib69","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/hmg\/ddi147","article-title":"Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease","volume":"14","author":"Van Raamsdonk","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib70","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1086\/318207","article-title":"Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in\u00a0vivo","volume":"68","author":"Leavitt","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib71","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nn.4014","article-title":"A SNP in the HTT promoter alters NF-kappaB binding and is a bidirectional genetic modifier of Huntington disease","volume":"18","author":"Becanovic","year":"2015","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.omtm.2022.03.001_bib72","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/nbt.2376","article-title":"Assessing unintended hybridization-induced biological effects of oligonucleotides","volume":"30","author":"Lindow","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2022.03.001_bib73","doi-asserted-by":"crossref","first-page":"10426","DOI":"10.1093\/nar\/gkt825","article-title":"Self-duplexing CUG repeats selectively inhibit mutant huntingtin expression","volume":"41","author":"Fiszer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2022.03.001_bib74","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.omtm.2022.03.001_bib75","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1093\/nar\/gkq1323","article-title":"Mutant CAG repeats of Huntingtin transcript fold into hairpins, form nuclear foci and are targets for RNA interference","volume":"39","author":"de Mezer","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2022.03.001_bib76","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.chembiol.2010.10.013","article-title":"Allele-selective inhibition of huntingtin expression by switching to an miRNA-like RNAi mechanism","volume":"17","author":"Hu","year":"2010","journal-title":"Chem. Biol."},{"key":"10.1016\/j.omtm.2022.03.001_bib77","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.omtm.2022.03.001_bib78","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.omtn.2019.12.012","article-title":"Universal RNAi triggers for the specific inhibition of mutant huntingtin, atrophin-1, ataxin-3, and ataxin-7 expression","volume":"19","author":"Kotowska-Zimmer","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.omtm.2022.03.001_bib79","doi-asserted-by":"crossref","first-page":"11270","DOI":"10.1093\/nar\/gks907","article-title":"Mechanism of allele-selective inhibition of huntingtin expression by duplex RNAs that target CAG repeats: function through the RNAi pathway","volume":"40","author":"Hu","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2022.03.001_bib80","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.cell.2012.08.002","article-title":"Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression","volume":"150","author":"Yu","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib81","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.omtm.2022.03.001_bib82","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/s41591-019-0478-3","article-title":"Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington's disease","volume":"25","author":"Zeitler","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2022.03.001_bib83","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/gtc.12730","article-title":"Evaluation of off-target effects of gapmer antisense oligonucleotides using human cells","volume":"24","author":"Yoshida","year":"2019","journal-title":"Genes Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib84","doi-asserted-by":"crossref","first-page":"8638","DOI":"10.1093\/nar\/gkv857","article-title":"In silico and in\u00a0vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization","volume":"43","author":"Kamola","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2022.03.001_bib85","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41593-018-0075-7","article-title":"Striatal neurons directly converted from Huntington's disease patient fibroblasts recapitulate age-associated disease phenotypes","volume":"21","author":"Victor","year":"2018","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.omtm.2022.03.001_bib86","doi-asserted-by":"crossref","first-page":"E762","DOI":"10.1073\/pnas.1715865115","article-title":"Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes","volume":"115","author":"Conforti","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.omtm.2022.03.001_bib87","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1042\/BJ20111495","article-title":"Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient","volume":"446","author":"Chae","year":"2012","journal-title":"Biochem. J."},{"key":"10.1016\/j.omtm.2022.03.001_bib88","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nn.4532","article-title":"Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice","volume":"20","author":"Consortium","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.omtm.2022.03.001_bib89","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1093\/hmg\/ddv080","article-title":"HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity","volume":"24","author":"Mattis","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib90","doi-asserted-by":"crossref","first-page":"6934","DOI":"10.1038\/s41598-021-85656-x","article-title":"The difficulty to model Huntington's disease in\u00a0vitro using striatal medium spiny neurons differentiated from human induced pluripotent stem cells","volume":"11","author":"Le Cann","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2022.03.001_bib91","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.stem.2012.04.027","article-title":"Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes","volume":"11","author":"Consortium","year":"2012","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.omtm.2022.03.001_bib92","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1002\/stem.1135","article-title":"Neuronal properties, in\u00a0vivo effects, and pathology of a Huntington's disease patient-derived induced pluripotent stem cells","volume":"30","author":"Jeon","year":"2012","journal-title":"Stem Cells"},{"key":"10.1016\/j.omtm.2022.03.001_bib93","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1093\/hmg\/ddq456","article-title":"Huntington's and myotonic dystrophy hESCs: down-regulated trinucleotide repeat instability and mismatch repair machinery expression upon differentiation","volume":"20","author":"Seriola","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib94","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S1472-6483(10)60053-3","article-title":"Human embryonic stem cell models of Huntington disease","volume":"19","author":"Niclis","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"10.1016\/j.omtm.2022.03.001_bib95","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/hmg\/dds397","article-title":"A fully humanized transgenic mouse model of Huntington disease","volume":"22","author":"Southwell","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2022.03.001_bib96","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1089\/hum.2020.323","article-title":"Allele-specific knockdown of mutant huntingtin protein via editing at coding region single nucleotide polymorphism heterozygosities","volume":"33","author":"Oikemus","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2022.03.001_bib97","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/bib\/bbq016","article-title":"Challenges of sequencing human genomes","volume":"11","author":"Koboldt","year":"2010","journal-title":"Brief. Bioinformatics"}],"container-title":["Molecular Therapy - Methods &amp; Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050122000298?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050122000298?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:30:46Z","timestamp":1762421446000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050122000298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":97,"alternative-id":["S2329050122000298"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2022.03.001","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington's disease","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2022.03.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors.","name":"copyright","label":"Copyright"}]}}