AVI-4658 is a phosphorodiamidate morpholino oligomer (PMO) designed to induce 
skipping of dystrophin exon 51 and restore its expression in patients with 
Duchenne muscular dystrophy (DMD). Preclinically, restoration of dystrophin in 
the dystrophic mdx mouse model requires skipping of exon 23, achieved with the 
mouse-specific PMO, AVI-4225. Herein, we report the potential toxicological 
consequences of exon skipping and dystrophin restoration in mdx mice using 
AVI-4225. We also evaluated the toxicological effects of AVI-4658 in both mdx 
and wild-type mice. In both studies, animals were dosed once weekly for 12 weeks 
up to the maximum feasible dose of 960 mg/kg per injection. Both AVI-4658 and 
AVI-4225 were well-tolerated at all doses. Findings in AVI-4225-treated animals 
were generally limited to mild renal tubular basophilia/vacuolation, without any 
significant changes in renal function and with evidence of reversing. No 
toxicity associated with the mechanism of action of AVI-4225 in a dystrophic 
animal was observed.