Here we demonstrate a dual gene therapy approach in a mouse model of OPMD by using RNA interference (RNAi) to inhibit the expression of all endogenous (that is, both wild type and expanded) PABPN1 and express a sequence-optimized normal PABPN1 resistant to RNAi-induced cleavage. This evidence concerns the gene PABPN1 and oculopharyngeal muscular dystrophy.