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Mutant CAG Repeats Effectively Targeted by RNA Interference in SCA7 Cells.

ABSTRACT: Spinocerebellar ataxia type 7 (SCA7) is a human neurodegenerative polyglutamine (polyQ) disease caused by a CAG repeat expansion in the open reading frame of the ATXN7 gene. The allele-selective silencing of mutant transcripts using a repeat-targeting strategy has previously been used for several polyQ diseases. Herein, we demonstrate that the selective targeting of a repeat tract in a mutant ATXN7 transcript by RNA interference is a feasible approach and results in an efficient decrease of mutant ataxin-7 protein in patient-derived cells. Oligonucleotides (ONs) containing specific base substitutions cause the downregulation of the ATXN7 mutant allele together with the upregulation of its normal allele. The A2 ON shows high allele selectivity at a broad range of concentrations and also restores UCHL1 expression, which is downregulated in SCA7.

SUBMITTER: Fiszer A

PROVIDER: S-EPMC5192508 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Mutant CAG Repeats Effectively Targeted by RNA Interference in SCA7 Cells.

Fiszer Agnieszka A Wroblewska Joanna P JP Nowak Bartosz M BM Krzyzosiak Wlodzimierz J WJ

Genes 20161217 12

Spinocerebellar ataxia type 7 (SCA7) is a human neurodegenerative polyglutamine (polyQ) disease caused by a CAG repeat expansion in the open reading frame of the <i>ATXN7</i> gene. The allele-selective silencing of mutant transcripts using a repeat-targeting strategy has previously been used for several polyQ diseases. Herein, we demonstrate that the selective targeting of a repeat tract in a mutant <i>ATXN7</i> transcript by RNA interference is a feasible approach and results in an efficient de ...[more]

PMID: 27999335

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