{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:48:26Z","timestamp":1791931706412,"version":"4.3.4"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32022015"],"award-info":[{"award-number":["32022015"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871295"],"award-info":[{"award-number":["31871295"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Training Program of the Major Research Plan of the National Natural Science Foundation of China","award":["92268120"],"award-info":[{"award-number":["92268120"]}]},{"name":"Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study","award":["SN-ZJU-SIAS-008"],"award-info":[{"award-number":["SN-ZJU-SIAS-008"]}]},{"name":"Provincial Natural Science Foundation of Jiangsu","award":["BK20230460"],"award-info":[{"award-number":["BK20230460"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["020814380146"],"award-info":[{"award-number":["020814380146"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["020814380162"],"award-info":[{"award-number":["020814380162"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Machado\u2013Joseph disease, also known as spinocerebellar ataxia type 3 (MJD\/SCA3), is a fatal autosomal dominant hereditary ataxia characterized by cerebellar ataxia resulting from the abnormal expansion of CAG repeats in exon 10 of the ATXN3 gene. At present, there is no effective treatment for SCA3. Small interfering RNAs (siRNAs) are emerging as potential therapeutic strategies to target the disease-causing mutant ATXN3 (mATXN3) protein specifically. However, the efficiency of delivery of siRNAs remains a major obstacle for clinical application, particularly in brain disorders.<\/jats:p>\n                  <jats:p>The aim of this study was to develop a synthetic biology strategy to reprogram the host liver as a tissue chassis to induce and deliver in vivo self-assembled siRNAs to target the ATXN3 gene. A synthetic construct directed by a cytomegalovirus promoter was designed to encode a neuron-targeting rabies virus glycoprotein tag and mATXN3-siRNA. After intravenous injection, the synthetic construct was taken up by mouse livers, which were then reprogrammed to enable the self-assembly, production and secretion of small extracellular vesicles encapsulating mATXN3-siRNA. The small extracellular vesicle-encapsulated mATXN3-siRNA was transported through the endogenous circulating system of small extracellular vesicles, crossing the blood\u2013brain barrier and reaching the cerebellar cortex and spinal cerebellar tract, where they silenced the ATXN3 gene.<\/jats:p>\n                  <jats:p>Treatment with the synthetic construct for 8 or 12 weeks led to significant improvements in motor balance ability and reduction of cerebellar atrophy in YACMJD84.2 transgenic mice. The number of Purkinje cells in the cerebellar cortex was significantly increased, and the loss of myelin basic protein was reduced. Moreover, the quantity of neurotoxic nuclear inclusion bodies and the expression of glial fibrillary acidic protein, which promotes neuroinflammation in activated astrocytes, were decreased significantly.<\/jats:p>\n                  <jats:p>The synthetic construct facilitated the generation and delivery of in vivo self-assembled siRNA to the cerebellar cortex and spinal cerebellar tract, thereby inhibiting the expression of mATXN3 protein. This treatment successfully addressed motor impairments, alleviated neuropathological phenotypes and mitigated neuroinflammation in YACMJD84.2 transgenic mice. Our strategy effectively overcomes the primary challenges associated with siRNA therapy for cerebellar ataxia, offering a promising avenue for future clinical treatments.<\/jats:p>","DOI":"10.1093\/brain\/awae304","type":"journal-article","created":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T07:14:57Z","timestamp":1726902897000},"page":"817-832","source":"Crossref","is-referenced-by-count":14,"title":["Treatment of neurological pathology and inflammation in Machado\u2013Joseph disease through\n                    <i>in vivo<\/i>\n                    self-assembled siRNA"],"prefix":"10.1093","volume":"148","author":[{"given":"Zhizong","family":"Li","sequence":"first","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]},{"name":"Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghu","family":"Du","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Nanjing University of Chinese Medicine , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penglu","family":"Chen","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yansheng","family":"Kan","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmeng","family":"Pan","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]},{"name":"Research Unit of Extracellular RNA, Chinese Academy of Medical Sciences , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8425-2867","authenticated-orcid":false,"given":"Zhong","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6756-7130","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]},{"name":"Research Unit of Extracellular RNA, Chinese Academy of Medical Sciences , Nanjing, Jiangsu 210023 ,","place":["China"]},{"name":"Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University , Nanjing, Jiangsu 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"2025030619374551900_awae304-B1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ng1194-221","article-title":"CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14Q32.1","volume":"8","author":"Kawaguchi","year":"1994","journal-title":"Nat Genet"},{"key":"2025030619374551900_awae304-B2","first-page":"S252","article-title":"The global epidemiology of hereditary ataxias and spastic paraplegias: A systematic review of prevalence studies","volume":"28","author":"Ruano","year":"2013","journal-title":"Mov Disord"},{"key":"2025030619374551900_awae304-B3","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nrn1474","article-title":"Pathways to motor incoordination: The inherited ataxias","volume":"5","author":"Taroni","year":"2004","journal-title":"Nat Rev Neurosci"},{"key":"2025030619374551900_awae304-B4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s12311-008-0013-4","article-title":"SCA3: Neurological features, pathogenesis and animal models","volume":"7","author":"Riess","year":"2008","journal-title":"Cerebellum"},{"key":"2025030619374551900_awae304-B5","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1093\/brain\/118.5.1077","article-title":"Detection of the Machado\u2013Joseph disease spinocerebellar ataxia 3 trinucleotide repeat expansion in families with autosomal dominant motor disorders, including the Drew family of Walworth","volume":"118","author":"Giunti","year":"1995","journal-title":"Brain"},{"key":"2025030619374551900_awae304-B6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/jnc.14541","article-title":"Machado\u2013Joseph disease\/spinocerebellar ataxia type 3: Lessons from disease pathogenesis and clues into therapy","volume":"148","author":"Matos","year":"2019","journal-title":"J Neurochem"},{"key":"2025030619374551900_awae304-B7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.pneurobio.2011.11.006","article-title":"Toward understanding Machado\u2013Joseph disease","volume":"97","author":"do Carmo Costa","year":"2012","journal-title":"Prog Neurobiol"},{"key":"2025030619374551900_awae304-B8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.omtn.2021.11.015","article-title":"Allele-specific targeting of mutant ataxin-3 by antisense oligonucleotides in SCA3-iPSC-derived neurons","volume":"27","author":"Hauser","year":"2022","journal-title":"Mol Ther Nucleic Acids"},{"key":"2025030619374551900_awae304-B9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.pneurobio.2015.06.004","article-title":"Toward therapeutic targets for SCA3: Insight into the role of Machado\u2013Joseph disease protein ataxin-3 in misfolded proteins clearance","volume":"132","author":"Li","year":"2015","journal-title":"Prog Neurobiol"},{"key":"2025030619374551900_awae304-B10","doi-asserted-by":"crossref","first-page":"e1004937","DOI":"10.1371\/journal.pgen.1004937","article-title":"Ataxin-3, DNA damage repair, and SCA3 cerebellar degeneration: On the path to parsimony?","volume":"11","author":"Ward","year":"2015","journal-title":"PLoS Genet"},{"key":"2025030619374551900_awae304-B11","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":"2025030619374551900_awae304-B12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.omtn.2017.04.005","article-title":"Evaluation of antisense oligonucleotides targeting ATXN3 in SCA3 mouse models","volume":"7","author":"Moore","year":"2017","journal-title":"Mol Ther Nucleic Acids"},{"key":"2025030619374551900_awae304-B13","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.biomaterials.2015.12.021","article-title":"Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype","volume":"82","author":"Concei\u00e7\u00e3o","year":"2016","journal-title":"Biomaterials"},{"key":"2025030619374551900_awae304-B14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.arr.2015.03.001","article-title":"siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery","volume":"21","author":"Gomes","year":"2015","journal-title":"Ageing Res Rev"},{"key":"2025030619374551900_awae304-B15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41572-019-0074-3","article-title":"Spinocerebellar ataxia","volume":"5","author":"Klockgether","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2025030619374551900_awae304-B16","doi-asserted-by":"crossref","first-page":"e44138","DOI":"10.1371\/journal.pone.0044138","article-title":"A novel in vivo siRNA delivery system specifically targeting liver cells for protection of ConA-induced fulminant hepatitis","volume":"7","author":"Jiang","year":"2012","journal-title":"PLoS One"},{"key":"2025030619374551900_awae304-B17","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1038\/mt.2013.144","article-title":"Toward RNAi therapy for the polyglutamine disease Machado\u2013Joseph disease","volume":"21","author":"Costa","year":"2013","journal-title":"Mol Ther"},{"key":"2025030619374551900_awae304-B18","doi-asserted-by":"crossref","first-page":"754","DOI":"10.5966\/sctm.2015-0197","article-title":"Mesenchymal stromal cell-derived extracellular vesicles protect the fetal brain after hypoxia-ischemia","volume":"5","author":"Ophelders","year":"2016","journal-title":"Stem Cells Transl Med"},{"key":"2025030619374551900_awae304-B19","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1038\/cr.2014.121","article-title":"Tumor-secreted miR-214 induces regulatory T cells: A major link between immune evasion and tumor growth","volume":"24","author":"Yin","year":"2014","journal-title":"Cell Res"},{"key":"2025030619374551900_awae304-B20","doi-asserted-by":"crossref","first-page":"23586","DOI":"10.1074\/jbc.M113.489302","article-title":"Microvesicle-mediated transfer of MicroRNA-150 from monocytes to endothelial cells promotes angiogenesis","volume":"288","author":"Li","year":"2013","journal-title":"J Biol Chem"},{"key":"2025030619374551900_awae304-B21","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.molcel.2010.06.010","article-title":"Secreted monocytic miR-150 enhances targeted endothelial cell migration","volume":"39","author":"Zhang","year":"2010","journal-title":"Mol Cell"},{"key":"2025030619374551900_awae304-B22","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"van Niel","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025030619374551900_awae304-B23","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1002\/wrna.1363","article-title":"Exosome-mediated small RNA delivery for gene therapy","volume":"7","author":"Zhou","year":"2016","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"2025030619374551900_awae304-B24","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.tibtech.2017.03.004","article-title":"Exosomes in cancer nanomedicine and immunotherapy: Prospects and challenges","volume":"35","author":"Syn","year":"2017","journal-title":"Trends Biotechnol"},{"key":"2025030619374551900_awae304-B25","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41422-021-00491-z","article-title":"In vivo self-assembled small RNAs as a new generation of RNAi therapeutics","volume":"31","author":"Fu","year":"2021","journal-title":"Cell Res"},{"key":"2025030619374551900_awae304-B26","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1093\/brain\/awab354","article-title":"Therapeutic reversal of Huntington\u2019s disease by in vivo self-assembled siRNAs","volume":"144","author":"Zhang","year":"2021","journal-title":"Brain"},{"key":"2025030619374551900_awae304-B27","doi-asserted-by":"crossref","first-page":"5700","DOI":"10.1038\/s41467-022-33436-0","article-title":"In vivo self-assembled siRNA as a modality for combination therapy of ulcerative colitis","volume":"13","author":"Zhou","year":"2022","journal-title":"Nat Commun"},{"key":"2025030619374551900_awae304-B28","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jconrel.2023.04.026","article-title":"In vivo self-assembled small RNA targets H19 lncRNA for the treatment of colorectal cancer","volume":"358","author":"Sun","year":"2023","journal-title":"J Control Release"},{"key":"2025030619374551900_awae304-B29","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/j.ymthe.2023.04.001","article-title":"Extracellular vesicle-based delivery of silencing sequences for the treatment of Machado-Joseph disease\/spinocerebellar ataxia type 3","volume":"31","author":"Rufino-Ramos","year":"2023","journal-title":"Mol Ther"},{"key":"2025030619374551900_awae304-B30","doi-asserted-by":"crossref","first-page":"1816710","DOI":"10.1080\/20013078.2020.1816710","article-title":"Fusion protein engineered exosomes for targeted degradation of specific RNAs in lysosomes: A proof-of-concept study","volume":"9","author":"Li","year":"2020","journal-title":"J Extracell Vesicles"},{"key":"2025030619374551900_awae304-B31","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1007\/s13311-021-01075-w","article-title":"DNAzyme cleavage of CAG repeat RNA in polyglutamine diseases","volume":"18","author":"Zhang","year":"2021","journal-title":"Neurotherapeutics"},{"key":"2025030619374551900_awae304-B32","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/ana.20141","article-title":"Sequence-dependent and independent inhibition specific for mutant ataxin-3 by small interfering RNA","volume":"56","author":"Li","year":"2004","journal-title":"Ann Neurol"},{"key":"2025030619374551900_awae304-B33","doi-asserted-by":"crossref","first-page":"7195","DOI":"10.1073\/pnas.1231012100","article-title":"Allele-specific silencing of dominant disease genes","volume":"100","author":"Miller","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025030619374551900_awae304-B34","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.freeradbiomed.2014.03.023","article-title":"Aqueous extract of Glycyrrhiza inflata inhibits aggregation by upregulating PPARGC1A and NFE2L2\u2013ARE pathways in cell models of spinocerebellar ataxia 3","volume":"71","author":"Chen","year":"2014","journal-title":"Free Radic Biol Med"},{"key":"2025030619374551900_awae304-B35","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.tibtech.2020.05.012","article-title":"Technologies and standardization in research on extracellular vesicles","volume":"38","author":"Gandham","year":"2020","journal-title":"Trends Biotechnol"},{"key":"2025030619374551900_awae304-B36","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nature20607","article-title":"Designed proteins induce the formation of nanocage-containing extracellular vesicles","volume":"540","author":"Votteler","year":"2016","journal-title":"Nature"},{"key":"2025030619374551900_awae304-B37","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1002\/mds.28140","article-title":"In vivo molecular signatures of cerebellar pathology in spinocerebellar ataxia type 3","volume":"35","author":"Costa","year":"2020","journal-title":"Mov Disord"},{"key":"2025030619374551900_awae304-B38","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1007\/s12035-018-1331-2","article-title":"Citalopram reduces aggregation of ATXN3 in a YAC transgenic mouse model of Machado-Joseph disease","volume":"56","author":"Ashraf","year":"2019","journal-title":"Mol Neurobiol"},{"key":"2025030619374551900_awae304-B39","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/j.1749-6632.1991.tb15608.x","article-title":"Posttranscriptional regulation of myelin protein gene expression","volume":"633","author":"Campagnoni","year":"1991","journal-title":"Ann N Y Acad Sci"},{"key":"2025030619374551900_awae304-B40","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00401-010-0717-7","article-title":"Axonal inclusions in spinocerebellar ataxia type 3","volume":"120","author":"Seidel","year":"2010","journal-title":"Acta Neuropathol"},{"key":"2025030619374551900_awae304-B41","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1136\/jnnp.66.2.222","article-title":"Age related axonal neuropathy in spinocerebellar ataxia type 3\/Machado-Joseph disease (SCA3\/MJD)","volume":"66","author":"Klockgether","year":"1999","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2025030619374551900_awae304-B42","doi-asserted-by":"crossref","first-page":"1182431","DOI":"10.3389\/fnmol.2023.1182431","article-title":"Viewpoint: Spinocerebellar ataxias as diseases of PPurkinje cell dysfunction rather than Purkinje cell loss","volume":"16","author":"Kapfhammer","year":"2023","journal-title":"Front Mol Neurosci"},{"key":"2025030619374551900_awae304-B43","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/jnen\/nlaa033","article-title":"Spinocerebellar ataxia type 3: A case report and literature review","volume":"79","author":"McCord","year":"2020","journal-title":"J Neuropathol Exp Neurol"},{"key":"2025030619374551900_awae304-B44","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s12311-020-01160-4","article-title":"Essential tremor within the broader context of other forms of cerebellar degeneration","volume":"19","author":"Louis","year":"2020","journal-title":"Cerebellum"},{"key":"2025030619374551900_awae304-B45","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.nbd.2005.07.011","article-title":"Polyglutamine-expanded ataxin-3 activates mitochondrial apoptotic pathway by upregulating Bax and downregulating Bcl-xL","volume":"21","author":"Chou","year":"2006","journal-title":"Neurobiol Dis"},{"key":"2025030619374551900_awae304-B46","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.3390\/cells12101404","article-title":"Tissue-specific vulnerability to apoptosis in Machado-Joseph disease","volume":"12","author":"Ferreira","year":"2023","journal-title":"Cells"},{"key":"2025030619374551900_awae304-B47","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/cdd.2017.186","article-title":"BCL-2 family proteins: Changing partners in the dance towards death","volume":"25","author":"Kale","year":"2018","journal-title":"Cell Death Differ"},{"key":"2025030619374551900_awae304-B48","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.pneurobio.2011.01.005","article-title":"GFAP in health and disease","volume":"93","author":"Middeldorp","year":"2011","journal-title":"Prog Neurobiol"},{"key":"2025030619374551900_awae304-B49","doi-asserted-by":"crossref","first-page":"10606","DOI":"10.3390\/ijms241310606","article-title":"Genetic ablation of inositol 1,4,5-trisphosphate receptor type 2 fails to modify disease progression in a mouse model of spinocerebellar ataxia type 3","volume":"24","author":"Cunha-Garcia","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025030619374551900_awae304-B50","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s12311-015-0667-7","article-title":"High serum GFAP levels in SCA3\/MJD may not correlate with disease progression","volume":"14","author":"Shi","year":"2015","journal-title":"Cerebellum"},{"key":"2025030619374551900_awae304-B51","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1523\/JNEUROSCI.21-15-05389.2001","article-title":"Inflammatory genes are upregulated in expanded ataxin-3-expressing cell lines and spinocerebellar ataxia type 3 brains","volume":"21","author":"Evert","year":"2001","journal-title":"J Neurosci"},{"key":"2025030619374551900_awae304-B52","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0896-6273(00)80943-5","article-title":"Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3","volume":"19","author":"Paulson","year":"1997","journal-title":"Neuron"},{"key":"2025030619374551900_awae304-B53","doi-asserted-by":"crossref","first-page":"e1004656","DOI":"10.1371\/journal.pcbi.1004656","article-title":"The siRNA non-seed region and its target sequences are auxiliary determinants of off-target effects","volume":"11","author":"Kamola","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"2025030619374551900_awae304-B54","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1261\/rna.25706","article-title":"Widespread siRNA \u201coff-target\u201d transcript silencing mediated by seed region sequence complementarity","volume":"12","author":"Jackson","year":"2006","journal-title":"RNA"},{"key":"2025030619374551900_awae304-B55","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3390\/genes13020319","article-title":"The siRNA off-target effect is determined by base-pairing stabilities of two different regions with opposite effects","volume":"13","author":"Kobayashi","year":"2022","journal-title":"Genes (Basel)."},{"key":"2025030619374551900_awae304-B56","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1232033","article-title":"RNA-guided human genome engineering via Cas9","volume":"339","author":"Mali","year":"2013","journal-title":"Science"},{"key":"2025030619374551900_awae304-B57","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat Protoc"},{"key":"2025030619374551900_awae304-B58","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1089\/scd.2017.0209","article-title":"CRISPR\/Cas9-targeted deletion of polyglutamine in spinocerebellar ataxia type 3-derived iPSCs","volume":"27","author":"Ouyang","year":"2018","journal-title":"Stem Cells Dev"},{"key":"2025030619374551900_awae304-B59","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1038\/mtna.2015.37","article-title":"Off-target effects in CRISPR\/Cas9-mediated genome engineering","volume":"4","author":"Zhang","year":"2015","journal-title":"Mol Ther Nucleic Acids"},{"key":"2025030619374551900_awae304-B60","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/nbt.4192","article-title":"Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements","volume":"36","author":"Kosicki","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2025030619374551900_awae304-B61","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1126\/scitranslmed.aaf5660","article-title":"An miRNA-mediated therapy for SCA6 blocks IRES-driven translation of the CACNA1A second cistron","volume":"8","author":"Miyazaki","year":"2016","journal-title":"Sci Transl Med"},{"key":"2025030619374551900_awae304-B62","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/s41587-019-0205-0","article-title":"A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system","volume":"37","author":"Alterman","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2025030619374551900_awae304-B63","doi-asserted-by":"crossref","first-page":"6099","DOI":"10.1093\/nar\/gkae368","article-title":"A programmable dual-targeting siRNA scaffold supports potent two-gene modulation in the central nervous system","volume":"52","author":"Belgrad","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"2025030619374551900_awae304-B64","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.bbrc.2007.08.062","article-title":"Inactivation of the mouse Atxn3 (ataxin-3) gene increases protein ubiquitination","volume":"362","author":"Schmitt","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"2025030619374551900_awae304-B65","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s12017-010-8137-3","article-title":"Mouse ataxin-3 functional knock-out model","volume":"13","author":"Switonski","year":"2011","journal-title":"Neuromolecular Med"},{"key":"2025030619374551900_awae304-B66","doi-asserted-by":"crossref","first-page":"e69782","DOI":"10.1371\/journal.pone.0069782","article-title":"The C57BL\/6J mouse exhibits sporadic congenital portosystemic shunts","volume":"8","author":"Cudalbu","year":"2013","journal-title":"PLoS One"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awae304\/59292842\/awae304.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/3\/817\/59292842\/awae304.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/3\/817\/59292842\/awae304.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T14:45:29Z","timestamp":1741272329000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/148\/3\/817\/7771322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,24]]},"references-count":66,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,9,24]]},"published-print":{"date-parts":[[2025,3,6]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awae304","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2024,9,24]]}}}