Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1.

ABSTRACT: Myotonic dystrophy type 1 (DM1) is a dominant genetic disease in which the expansion of long CTG trinucleotides in the 3' UTR of the myotonic dystrophy protein kinase (DMPK) gene results in toxic RNA gain-of-function and gene mis-splicing affecting mainly the muscles, the heart, and the brain. The CUG-expanded transcripts are a suitable target for the development of antisense oligonucleotide (ASO) therapies. Various chemical modifications of the sugar-phosphate backbone have been reported to significantly enhance the affinity of ASOs for RNA and their resistance to nucleases, making it possible to reverse DM1-like symptoms following systemic administration in different transgenic mouse models. However, specific tissue delivery remains to be improved to achieve significant clinical o

SUBMITTER: De Serres-Berard T 

PROVIDER: S-EPMC9657934 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature