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Objective  Spinocerebellar ataxia type 1 is an autosomal dominant fatal neurodegenerative disease caused by a polyglutamine expansion in the coding region of  ATXN1 . We showed previously that partial suppression of mutant ataxin‐1 (ATXN1) expression, using virally expressed RNAi triggers, could prevent disease symptoms in a transgenic mouse model and a knockin mouse model of the disease, using a single dose of virus. Here, we set out to test whether RNAi triggers targeting  ATXN1  could not only prevent, but also reverse disease readouts when delivered after symptom onset.    Methods  We administered recombinant adeno‐associated virus (rAAV) expressing miS1, an artificial miRNA targeting human  ATXN1  mRNA (rAAV.miS1), to a mouse model of spinocerebellar ataxia type 1 (SCA1; B05 mice). Viruses were delivered prior to or after symptom onset at multiple doses. Control B05 mice were treated with rAAVs expressing a control artificial miRNA, or with saline. Animal behavior, molecular phenotypes, neuropathology, and magnetic resonance spectroscopy were done on all groups, and data were compared to wild‐type littermates.    Results  We found that SCA1 phenotypes could be reversed by partial suppression of human mutant  ATXN1  mRNA by rAAV.miS1 when delivered after symptom onset. We also identified the therapeutic range of rAAV.miS1 that could prevent or reverse disease readouts.    Interpretation  SCA1 disease may be reversible by RNAi therapy, and the doses required for advancing this therapy to humans are delineated. Ann Neurol 2016;80:754–765

RNAi prevents and reverses phenotypes induced by mutant human ataxin‐1