Figure 3. Recovery of dystrophin expression by in vivo intramuscular injection of a three-AO cocktail, but not Ex6A alone.

(A) Restoration of dystrophin expression in TA at 14 days after single injection with 1.2 mg of Ex6A only, or cocktail containing 0.12 mg each, 0.6 mg each, or 1.2 mg each of antisense morpholino Ex6A, Ex6B, and Ex8A are shown. Age-matched non-treated CXMD (NT) and wild-type (WT) dogs are shown as controls. HE staining at 14 days after 1.2 mg each of the cocktail injection and age-matched non-treated control (NT) with consecutive cryosection stained with DYS-1 and DAPI show histological correction of the dystrophy. Bar; 100 μm.

(B) and (C) show the number of dystrophin (DYS1) positive fibers in TA or extensor carpi ulnaris at 14 days after a single injection with cocktail (Ex6A+Ex6B+Ex8A), or indicated combinations, at 1.2 mg each (morpholino; B), or 120 μg each 2'O-MePs (C). Values are mean ± s. e. m. (D) RT-PCR analysis at 2 weeks after intramuscular injection of cocktail or Ex6A morpholino at 1.2 mg each. The percentage of the in-frame exons 5-10 skip is shown under the gel image for treated muscle; normal control (WT) muscle shows the normal full-length in-frame transcript at the expected 100%.