This chemical modification increases RNA affinity, hydrophobicity, nuclease resistance for both phosphate and thiophosphate internucleotide linkages, and tcDNA-AONs do not activate RNase H. Systemic delivery of tcDNA-AONs induce high dystrophin rescue in skeletal muscles, heart and low levels in the brain, with amelioration of cardio-respiratory functions and DMD phenotype. Here, DMD is linked to Duchenne muscular dystrophy.