Design of RNAi hairpins for mutation-specific silencing of ataxin-7 and correction of a SCA7 phenotype.

ABSTRACT: Spinocerebellar ataxia type 7 is a polyglutamine disorder caused by an expanded CAG repeat mutation that results in neurodegeneration. Since no treatment exists for this chronic disease, novel therapies such post-transcriptional RNA interference-based gene silencing are under investigation, in particular those that might enable constitutive and tissue-specific silencing, such as expressed hairpins. Given that this method of silencing can be abolished by the presence of nucleotide mismatches against the target RNA, we sought to identify expressed RNA hairpins selective for silencing the mutant ataxin-7 transcript using a linked SNP. By targeting both short and full-length tagged ataxin-7 sequences, we show that mutation-specific selectivity can be obtained with single nucleotide mismatches

SUBMITTER: Scholefield J 

PROVIDER: S-EPMC2747278 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature