Antisense oligonucleotides: rising stars in eliminating RNA toxicity in myotonic dystrophy.

Myotonic dystrophy (DM) is a dominantly inherited, multisystemic disease caused by expanded CTG (type 1, DM1) or CCTG (type 2, DM2) repeats in untranslated regions of the mutated genes. Pathogenesis results from expression of RNAs from the mutated alleles that are toxic because of the expanded CUG or CCUG repeats. Increased understanding of the repeat-containing RNA (C/CUG(exp) RNA)-induced toxicity has led to the development of multiple strategies targeting the toxic RNA. Among these approaches, antisense oligonucleotides (ASOs) have demonstrated high potency in reversing the RNA toxicity in both cultured DM1 cells and DM1 animal models, thus offering great promise for the potential treatment of DM1. ASO targeting approaches will also provide avenues for the treatment of other repeat RNA-mediated diseases.