RNAi or overexpression: Alternative therapies for Spinocerebellar Ataxia Type 1

Neurobiology of Disease

Ryan L. Boudreau¹  Beverly L. Davidson¹  James C. Geoghegan¹  Megan S. Keiser²  Kim A. Lennox³ 

[1] Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA;Department of the Neuroscience Training Program, University of Iowa, Iowa City, IA 52242, USA;Integrated DNA Technologies Inc., Coralville, IA 52241, USA;

关键词: Spinocerebellar Ataxia Type 1;    Ataxin-1;    Ataxin-1-like;    miRNA;    RNAi;    AAV;   

DOI  :  

来源: DOAJ

【 摘 要 】

Spinocerebellar Ataxia Type 1 (SCA1) is an autosomal dominant late onset neurodegenerative disease caused by an expanded polyglutamine tract in ataxin-1. Here, we compared the protective effects of overexpressing ataxin-1-like using recombinant AAVs, or reducing expression of mutant ataxin-1 using virally delivered RNA interference (RNAi), in a transgenic mouse model of SCA1. For the latter, we used an artificial microRNA (miR) design that optimizes potency, efficacy and safety to suppress ataxin-1 expression (miS1). Delivery of either ataxin-1-like or miS1 viral vectors to SCA1 mice cerebella resulted in widespread cerebellar Purkinje cell transduction and improved behavioral and histological phenotypes. Our data indicate the utility of either approach as a possible therapy for SCA1 patients.

【 授权许可】

Unknown