Three Becker-inspired dystrophin nano-constructs, representing strong AON-therapy candidates, were examined with force and structural probes. These extensibility and folding studies focused on the altered linker regions introduced by their respective exon deletion(s). Results show that these linker regions fold into stable, spectrin-like domains. Further investigations into the structural dissimilarity among these three nano-constructs and wild-type dystrophin show that the linker regions of two nano-constructs are less stable, and the increased flexibility may impart functionality to these truncated BMD proteins. Structural principles gleaned from these studies were used to design a novel dystrophin construct with increased therapeutic function.