Mutant CAG Repeats Effectively Targeted by RNA Interference in SCA7 Cells

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2016 Dec 22

PMID 27999335

Citations 11

Authors

Agnieszka Fiszer

Joanna P Wroblewska

Bartosz M Nowak

Wlodzimierz J Krzyzosiak

Affiliations

Soon will be listed here.

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 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 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 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 expression, which is downregulated in SCA7.

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