Skip to main content
. 2021 Dec 10;50(1):17–34. doi: 10.1093/nar/gkab1199

Figure 1.

Figure 1.

Palmitic acid conjugation enhances the biodistribution and efficacy of tcDNA-ASO. (A) Sequences of the different tcDNA-ASOs and schematic design representing the conjugation of the palmitic acid at the 5’ end of tcDNA (tcDNA-PO, tcDNA-PS) using a C6-amino linker and a PS bond. (B) Experimental pharmacokinetics protocol (upper panel): mdx mice received a single intravenous dose of 10 μmol/kg of unconjugated (tcDNA-PO or tcDNA-PS) or conjugated tcDNA (palm-tcDNA-PO or palm-tcDNA-PS) and blood samples were collected at different time points (t = 0, 0.08 h (i.e. 5 min), 0.33 h (i.e. 15 min), 0.5 h (i.e. 30 min), 1, 4, 8, 16 and 24 h) after the administration. Semi-log plots of serum concentration of each tcDNA-ASO versus time from mice treated with 10 μmol/kg of unconjugated (tcDNA-PO or tcDNA-PS) or conjugated tcDNA (palm-tcDNA-PO or palm-tcDNA-PS). Data are represented as mean, n = 3/time point). (C) Quantification of tcDNA-ASO content in various tissues by fluorescent hybridization assay following a 4-week treatment at the dose of 10 μmol/kg/week. D) Detection of exon 23–skipped dystrophin mRNA by nested RT-PCR (right) and quantification of exon 23 skipping levels by qRT-PCR (bottom) in the different muscle tissues following a 4-week treatment at the dose of 10 μmol/kg/week (TA: tibialis anterior, gas: gastrocnemius, quad: quadriceps, Tri: triceps, Bi: biceps; Dia: diaphragm). Results are expressed as mean ± SEM; n = 4 mice per group.