Fig. 7: Parallel PNAs as brother strand (BS) have identical effect on ssASO. | Nature Communications

Fig. 7: Parallel PNAs as brother strand (BS) have identical effect on ssASO.

From: Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry

Fig. 7

Molecular modeling of Acsl1/parallel PNA a duplex constructed by optimization using the GFN1-XTB method (Supplementary Fig. 18 and Supplementary Data 3). b–e Mouse was subjected to a single subcutaneous injection of indicated ssASO and BROs at a dose of 150 nmol/kg. Melting temperatures of duplexes indicated (n = 3 independent experiments) (b). Acsl1 mRNA expression and ALT levels (n = 3 biologically independent samples; one-way ANOVA followed by two-sided Dunnett’s multiple comparison tests comparing to Acsl1, p values from left side; Acsl1 mRNA: <0.0001, 0.6407, 0.6986, 0.0144, 0.0002, <0.0001; ALT: 0.0002, 0.0059, 0.0007, 0.0002, 0.0002, 0.0002) (c), liver weight (n = 3 biologically independent samples; one-way ANOVA followed by two-sided Dunnett’s multiple comparison tests comparing to control, p values from left side; 0.0096, 0.0014, 0.0760, 0.0308, 0.9996, 0.3554) (d), and liver cytokine mRNA levels (n = 3 biologically independent samples; two-way ANOVA followed by two-sided Dunnett’s multiple comparison tests comparing to control, p values from left side; <0.0001, 0.0572, 0.1375, 0.0004, 0.4732, 0.1077, 0.3809, 0.9160, 0.9453, 0.6497, 0.3958, 0.6092) (e) were evaluated 96 h after administration. f Identification of liver-derived proteins bound by CBB staining for Acsl1b or Acsl1b/pPNA(C14−18) BROs. Data in Fig. 7b–e are presented as mean values ± SD. **p < 0.01, *p < 0.05. “ns” indicates not significant (p > 0.05). Source data are provided as a Source Data file.

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