Therapeutic potential of highly functional codon‑optimized microutrophin for muscle‑specific expression

Abstract

High expectations have been set on gene therapy with an AAV-delivered shortened version of dystrophin (μDys) for Duchenne muscular dystrophy (DMD), with several drug candidates currently undergoing clinical trials. Safety concerns with this therapeutic approach include the immune response to introduced dystrophin antigens observed in some DMD patients. Recent reports highlighted microutrophin (μUtrn) as a less immunogenic functional dystrophin substitute for gene therapy. In the current study, we created a human codon-optimized μUtrn which was subjected to side-by-side characterization with previously reported mouse and human μUtrn sequences after rAAV9 intramuscular injections in mdx mice