000108509 001__ 108509
000108509 005__ 20230519145417.0
000108509 0247_ $$2doi$$a10.1126/sciadv.abi6896
000108509 0248_ $$2sideral$$a125124
000108509 037__ $$aART-2021-125124
000108509 041__ $$aeng
000108509 100__ $$aLim, Wooi F
000108509 245__ $$aGene therapy with AR isoform 2 rescues spinal and bulbar muscular atrophy phenotype by modulating AR transcriptional activity
000108509 260__ $$c2021
000108509 5060_ $$aAccess copy available to the general public$$fUnrestricted
000108509 5203_ $$aSpinal 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
000108509 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000108509 590__ $$a14.98$$b2021
000108509 591__ $$aMULTIDISCIPLINARY SCIENCES$$b7 / 74 = 0.095$$c2021$$dQ1$$eT1
000108509 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000108509 700__ $$aForouhan, Mitra
000108509 700__ $$aRoberts, Thomas C
000108509 700__ $$aDabney, Jesse
000108509 700__ $$aEllerington, Ruth
000108509 700__ $$aSpeciale, Alfina A
000108509 700__ $$0(orcid)0000-0002-7477-8742$$aManzano, Raquel$$uUniversidad de Zaragoza
000108509 700__ $$aLieto, Maria
000108509 700__ $$aSangha, Gavinda
000108509 700__ $$aBanerjee, Subhashis
000108509 700__ $$aConceição, Mariana
000108509 700__ $$aCravo, Lara
000108509 700__ $$aBiscans, Annabelle
000108509 700__ $$aRoux, Loïc
000108509 700__ $$aPourshafie, Naemeh
000108509 700__ $$aGrunseich, Christopher
000108509 700__ $$aDuguez, Stephanie
000108509 700__ $$aKhvorova, Anastasia
000108509 700__ $$aPennuto, Maria
000108509 700__ $$aCortes, Constanza J
000108509 700__ $$aLa Spada, Albert R
000108509 700__ $$aFischbeck, Kenneth H
000108509 700__ $$aWood, Matthew JA
000108509 700__ $$aRinaldi, Carlo
000108509 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000108509 773__ $$g7, 34 (2021), eabi6896 [15 pp.]$$pSci. adv.$$tScience advances$$x2375-2548
000108509 8564_ $$s6770326$$uhttps://zaguan.unizar.es/record/108509/files/texto_completo.pdf$$yVersión publicada
000108509 8564_ $$s3642830$$uhttps://zaguan.unizar.es/record/108509/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000108509 909CO $$ooai:zaguan.unizar.es:108509$$particulos$$pdriver
000108509 951__ $$a2023-05-18-14:01:27
000108509 980__ $$aARTICLE