Stabilization of expanded (CTG)•(CAG) repeats by antisense oligonucleotides.

ABSTRACT: Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the gene DMPK. The expansion is highly unstable in somatic cells, a feature that may contribute to disease progression. The RNA expressed from the mutant allele exerts a toxic gain of function, due to the presence of an expanded CUG repeat (CUG(exp)). This RNA dominant mechanism is amenable to therapeutic intervention with antisense oligonucleotides (ASOs). For example, CAG-repeat ASOs that bind CUG(exp) RNA are beneficial in DM1 models by altering the protein interactions or metabolism of the toxic RNA. Because CUG(exp) RNA has been shown to aggravate instability of expanded CTG repeats, we studied whether CAG-repeat ASOs may also affect this aspect of DM1. In human cells the instability of (CTG)(800) was suppressed

SUBMITTER: Nakamori M 

PROVIDER: S-EPMC3242663 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature