Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs.

ABSTRACT: Expanded trinucleotide repeats cause many neurological diseases. These include Machado-Joseph disease (MJD) and Huntington's disease (HD), which are caused by expanded CAG repeats within an allele of the ataxin-3 (ATXN3) and huntingtin (HTT) genes, respectively. Silencing expression of these genes is a promising therapeutic strategy, but indiscriminate inhibition of both the mutant and wild-type alleles may lead to toxicity, and allele-specific approaches have required polymorphisms that differ among individuals. We report that peptide nucleic acid and locked nucleic acid antisense oligomers that target CAG repeats can preferentially inhibit mutant ataxin-3 and HTT protein expression in cultured cells. Duplex RNAs were less selective than single-stranded oligomers. The activity of the pept

SUBMITTER: Hu J 

PROVIDER: S-EPMC2765218 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature