Evaluation of eluforsen, a novel RNA oligonucleotide for restoration of CFTR function in in vitro and murine models of p.Phe508del cystic fibrosis
Fig 3
In vivo imaging and post-mortem detection demonstrate systemic exposure after OT administration of labeled eluforsen.
(A) Representative confocal images of lung paraffin sections of wild-type (WT) mice following a single OT administration of 10 mg/kg Cy5-labeled eluforsen (shown in red) and killed after 24 hours, 48 hours, 3 days, 7 days, and 14 days. The cell nucleus was stained with DAPI (shown in blue). Macrophages accumulate the Cy5-labeled eluforsen and are visible as highly fluorescent spherical cells (as indicated with the yellow arrows). (B) (i) Representative in vivo images at several time points showing the IRDye800 (CW800) signal from IRDye800-labeled eluforsen in green. Systemic exposure could be detected at 1 hour after administration. (ii) Mice were killed after 7 days and representative in situ images demonstrate a strong IRDye800 signal in the lungs. (iii) High-resolution post-mortem scans of organs from all animals show extrapulmonary distribution of eluforsen. Controls include a mouse that received an equimolar dose or IRDye800 alone (CW800) or unlabeled eluforsen. Mouse M1 shown (see S4 Fig for additional animals).