tc-DNA-HSA gapmer

tc-DNA-HSA gapmer is a preclinical tricyclo-DNA (tc-DNA) antisense oligonucleotide (ASO) gapmer designed to target mutant human skeletal actin (HSA) transcripts containing expanded CUG repeats (CUGexp). Developed by SQY Therapeutics in collaboration with Sorbonne Université, INSERM, the Institut de Myologie, and the Université de Versailles Saint-Quentin-en-Yvelines, this conformationally constrained DNA analog recruits RNase H to degrade pathogenic CUGexp-RNA. In mouse models of myotonic dystrophy type 1 (DM1), systemic administration of the tc-DNA-HSA gapmer has demonstrated near-complete degradation of toxic CUGexp-RNA, reduction of nuclear foci, correction of alternative splicing defects, and suppression of myotonia, highlighting its potential as a therapeutic approach for DM1.