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dc.contributor.authorLim, Wooi F.
dc.contributor.authorBiscans, Annabelle
dc.contributor.authorKhvorova, Anastasia
dc.contributor.authorRinaldi, Carlo
dc.date2022-08-11T08:10:01.000
dc.date.accessioned2022-08-23T16:52:43Z
dc.date.available2022-08-23T16:52:43Z
dc.date.issued2021-08-20
dc.date.submitted2022-03-24
dc.identifier.citation<p>Lim WF, Forouhan M, Roberts TC, Dabney J, Ellerington R, Speciale AA, Manzano R, Lieto M, Sangha G, Banerjee S, Conceição M, Cravo L, Biscans A, Roux L, Pourshafie N, Grunseich C, Duguez S, Khvorova A, Pennuto M, Cortes CJ, La Spada AR, Fischbeck KH, Wood MJA, Rinaldi C. Gene therapy with AR isoform 2 rescues spinal and bulbar muscular atrophy phenotype by modulating AR transcriptional activity. Sci Adv. 2021 Aug 20;7(34):eabi6896. doi: 10.1126/sciadv.abi6896. PMID: 34417184; PMCID: PMC8378820. <a href="https://doi.org/10.1126/sciadv.abi6896">Link to article on publisher's site</a></p>
dc.identifier.issn2375-2548 (Linking)
dc.identifier.doi10.1126/sciadv.abi6896
dc.identifier.pmid34417184
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42111
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractSpinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset neuromuscular condition caused by an abnormal polyglutamine (polyQ) tract expansion in androgen receptor (AR) protein. SBMA is a disease with high unmet clinical need. Recent studies have shown that mutant AR-altered transcriptional activity is key to disease pathogenesis. Restoring the transcriptional dysregulation without affecting other AR critical functions holds great promise for the treatment of SBMA and other AR-related conditions; however, how this targeted approach can be achieved and translated into a clinical application remains to be understood. Here, we characterized the role of AR isoform 2, a naturally occurring variant encoding a truncated AR lacking the polyQ-harboring domain, as a regulatory switch of AR genomic functions in androgen-responsive tissues. Delivery of this isoform using a recombinant adeno-associated virus vector type 9 resulted in amelioration of the disease phenotype in SBMA mice by restoring polyQ AR-dysregulated transcriptional activity.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34417184&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectspinal and bulbar muscular atrophy
dc.subjectandrogen receptor protein
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCongenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subjectGenetics and Genomics
dc.subjectMusculoskeletal Diseases
dc.subjectNervous System Diseases
dc.subjectTherapeutics
dc.titleGene therapy with AR isoform 2 rescues spinal and bulbar muscular atrophy phenotype by modulating AR transcriptional activity
dc.typeJournal Article
dc.source.journaltitleScience advances
dc.source.volume7
dc.source.issue34
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5947&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4913
dc.identifier.contextkey28414060
refterms.dateFOA2022-08-23T16:52:43Z
html.description.abstract<p>Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset neuromuscular condition caused by an abnormal polyglutamine (polyQ) tract expansion in androgen receptor (AR) protein. SBMA is a disease with high unmet clinical need. Recent studies have shown that mutant AR-altered transcriptional activity is key to disease pathogenesis. Restoring the transcriptional dysregulation without affecting other AR critical functions holds great promise for the treatment of SBMA and other AR-related conditions; however, how this targeted approach can be achieved and translated into a clinical application remains to be understood. Here, we characterized the role of AR isoform 2, a naturally occurring variant encoding a truncated AR lacking the polyQ-harboring domain, as a regulatory switch of AR genomic functions in androgen-responsive tissues. Delivery of this isoform using a recombinant adeno-associated virus vector type 9 resulted in amelioration of the disease phenotype in SBMA mice by restoring polyQ AR-dysregulated transcriptional activity.</p>
dc.identifier.submissionpathoapubs/4913
dc.contributor.departmentRNA Therapeutics Institute
dc.source.pageseabi6896


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Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY)
Except where otherwise noted, this item's license is described as Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY)