Fig. 5

In vivo delivery and suppression with ACE-tRNA as cDNA and RNA. a Representative images of mice injected with NLuc-UGA with ACE-tRNA^Arg (Arg-chr9.trna6 UGA) or pUC57 empty vector, NLuc-WT or water in the tibialis anterior muscle followed by electroporation at days 1, 2, and 7 after DNA administration. b Quantification of luminescence emission by the tibialis anterior muscles of the abovementioned mouse groups at different timepoints after DNA injection and electroporation (n = 3 mice per group, data are shown as SEM). c Rescued luminesce of stably expressed NLuc–UGA following transfection of Trpchr17.trna39cRNA and Glychr19.trna2 RNA transcripts (n = 3 for each ACE-tRNA). d Representative western blot analysis of CFTR protein expressed in HEK293 cells 36 h following transfection of WT, G542X, G542X + Glychr19.trna2, W1282X and W1282X + Trpchr17.trna39 CFTR cDNA. e Exemplar families of CFTR Cl^- current traces recorded using two-electrode voltage-clamp, 36 h following injection with WT, G542X, G542X + ACE-tRNA-Glychr19.trna2, W1282X and W1282X + ACE-tRNA-Trpchr17.trna39 CFTR cRNA. Currents were elicited using 5 mV voltage steps from −60 to +35 mV. The vertical and horizontal scale bars indicate 10 µA and 50 ms, respectively. f Dose response of G542X ACE-tRNA^Gly (filled circles; n = 11–19) and W1282X ACE-tRNA^Trp (open squares; n = 17–22) rescue (CFTR Cl^- currents elicited at +35 mV were normalized to WT CFTR Cl^- currents at +35 mV). ACE-tRNA^Gly rescue achieves WT-level of expressed CFTR current. Data is presented as standard error of mean for panels c and f