108509 20230519145417.0 doi 10.1126/sciadv.abi6896 sideral 125124 ART-2021-125124 eng Lim, Wooi F Gene therapy with AR isoform 2 rescues spinal and bulbar muscular atrophy phenotype by modulating AR transcriptional activity 2021 Access copy available to the general public Unrestricted 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 regu-latory switch of AR genomic functions in androgen-responsive tissues. Delivery of this isoform using a recombi-nant adeno-associated virus vector type 9 resulted in amelioration of the disease phenotype in SBMA mice by restoring polyQ AR–dysregulated transcriptional activity info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 14.98 2021 MULTIDISCIPLINARY SCIENCES 7 / 74 = 0.095 2021 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Forouhan, Mitra Roberts, Thomas C Dabney, Jesse Ellerington, Ruth Speciale, Alfina A Manzano, Raquel Universidad de Zaragoza (orcid)0000-0002-7477-8742 Lieto, Maria Sangha, Gavinda Banerjee, Subhashis Conceição, Mariana Cravo, Lara Biscans, Annabelle Roux, Loïc Pourshafie, Naemeh Grunseich, Christopher Duguez, Stephanie Khvorova, Anastasia Pennuto, Maria Cortes, Constanza J La Spada, Albert R Fischbeck, Kenneth H Wood, Matthew JA Rinaldi, Carlo 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 7, 34 (2021), eabi6896 [15 pp.] Sci. adv. Science advances 2375-2548 6770326 http://zaguan.unizar.es/record/108509/files/texto_completo.pdf Versión publicada 3642830 http://zaguan.unizar.es/record/108509/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:108509 articulos driver 2023-05-18-14:01:27 ARTICLE