image: GLP1R-dependent uptake of ASO and knockdown of gene expression in mice treated with eGLP1-ASO conjugates in vivo. (A) Representative pancreatic sections stained for ASO by IHC and MALAT1 RNA by ISH from mice treated for 2 weeks with three subcutaneous injections of (a) saline, (b) MALAT1-ASO (1 μmol/kg), or (c) eGLP1-MALAT1-ASO (1 μmol/kg). (B) ASO uptake by IHC and MALAT1 RNA levels by ISH in pancreatic sections from mice treated for 2 weeks with three intravenous injections of (a) saline or (b) eGLP1-MALAT1-ASO (1 μmol/kg). (C) MALAT1 gene expression by ISH in (a) wild-type (WT) and (b) GLP1R knockout (KO) mice 72 hours after a single subcutaneous dose of saline or eGLP1-MALAT1-ASO (1 μmol/kg). (D) Pancreatic section from wild-type mice stained using fluorescence in situ probes for MALAT1 (purple, arrows), insulin (green), and glucagon (red). Pancreatic sections were collected 72 hours after one subcutaneous administration of (a) saline or (b) MALAT1-ASO and (c) eGLP1-control-ASO or (d) eGLP1-MALAT1-ASO, and all compounds were dosed at 1 μmol/kg. Scale bars, 200 μm. Islets are circled in blue in (A) to (C). This material relates to a paper that appeared in the Oct. 17th, 2018, issue of Science Advances, published by AAAS. The paper, by C. Ämmälä at AstraZeneca in Gothenburg, Sweden, and colleagues was titled, "Targeted delivery of antisense oligonucleotides to pancreatic β-cells." view more
Credit: [Credit: Ämmälä <em>et al.</em>, <i>Sci. Adv</i>. 2018; 4 : eaat3386]