{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["37(1)"],"submitter":["Smith VL"],"pubmed_abstract":["Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from a CAG repeat expansion in the atrophin-1 (<i>ATN1</i>) gene. Because DRPLA, like many repeat expansion disorders (REDs), arises predominantly from toxic gain-of-function mechanisms, we hypothesized that <i>ATN1</i> knockdown would have therapeutic potential. To test this, we established the first fully humanized mouse model of a RED, in which one allele of mouse <i>Atn1</i> is completely replaced by human <i>ATN1</i>, including 112 pure CAG repeats. This novel approach to exploring RED biology provides significant advantages, notably the ability to test sequence-specific therapeutics targeting human sequences, even in introns and untranslated regions of pre-mRNA. We found that our model-the <i>At"],"journal":["Molecular therapy. Nucleic acids"],"pagination":["102815"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12857545"],"repository":["biostudies-literature"],"pubmed_title":["Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model."],"pmcid":["PMC12857545"],"pubmed_authors":["Greenfield J","Ben-Varon A","Khurana V","Zhao HT","Barker-Haliski M","Child DD","Carroll JB","Gidi BZ","Compton A","Cantle JP","Kordasiewicz HB","Yu T","Smith VL","Noble B","Gemos A","Prades S","Bragg RM","Korecka JA"],"additional_accession":[]},"is_claimable":false,"name":"Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model.","description":"Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from a CAG repeat expansion in the atrophin-1 (<i>ATN1</i>) gene. Because DRPLA, like many repeat expansion disorders (REDs), arises predominantly from toxic gain-of-function mechanisms, we hypothesized that <i>ATN1</i> knockdown would have therapeutic potential. To test this, we established the first fully humanized mouse model of a RED, in which one allele of mouse <i>Atn1</i> is completely replaced by human <i>ATN1</i>, including 112 pure CAG repeats. This novel approach to exploring RED biology provides significant advantages, notably the ability to test sequence-specific therapeutics targeting human sequences, even in introns and untranslated regions of pre-mRNA. We found that our model-the <i>At","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Mar","modification":"2026-06-18T05:48:05.49Z","creation":"2026-06-18T03:07:30.357Z"},"accession":"S-EPMC12857545","cross_references":{"pubmed":["41624332"],"doi":["10.1016/j.omtn.2025.102815"]}}