Fig. 3
Imaging therapeutic antisense oligonucleotide drug activity in vivo. We administered a CAG repeat morpholino (CAG) ASO designed to bind and neutralize the pathogenic effects of expanded CUG repeat RNA7 by intramuscular injection of the right gastrocnemius in TR;HSALR mice (N = 3). The left gastrocnemius was injected with saline or was untreated. a Representative images of quantitative in vivo DsRed and GFP fluorescence under general anesthesia 28 days after injection of the CAG ASO. Fluorescence intensity range = 0–4095 grayscale units. Bars = 4 mm. b Quantitative DsRed/GFP fluorescence ratios in muscles of untreated (black circles) and CAG ASO-treated (blue triangles) mice by serial in vivo imaging. Error bars indicate mean ± s.e.m. Non-linear regression. c RT-PCR analysis of transgene and endogenous Atp2a1 exon 22 in untreated (−) or CAG ASO-treated ( + ) muscles 49 days after injection. E empty lane, L DNA ladder, bp base pairs. d Quantitation of splicing results in c. Error bars indicate mean ± s.e.m. ***P = 0.0002; *P = mean difference 14.2, 95% CI of difference 1.0–27.5 (two-way ANOVA). These results are representative of four independent experiments
