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. 2019 Feb 26;16:194–205. doi: 10.1016/j.omtn.2019.02.013

Figure 2.

Figure 2

Extensive siRNA Chemical Modification Is Required to Induce RNAi Activity and Avoid an Immune Response

(A) Mice were dosed intratracheally with 50 mg/kg siRNA chemically modified (si-Ctnnb1 2′-F/OMe) or minimally modified (si-Ctnnb1 2′-OH) targeting the same nucleotide primary sequence. Plot represents Ctnnb1 mRNA in total lung relative to Ppib control 72 h after intratracheal dosing. Lines indicate means ± SE. (B) BAL neutrophil content after intratracheal dosing of PBS (empty circles), si-Ctnnb1 2′-F/OMe (filled circles), si-Ctnnb1 2′-OH (filled triangles), and LPS (empty triangles). (C) BAL cytokine levels were measured using the BD cytometric bead array (CBA) kit. Discontinued lines represent lower limit of detection (LOD). Data are means + SE. *p < 0.05, **p < 0.005, ***p < 0.001 versus PBS-treated mice, #p < 0.001, ##p < 0.005; n.s., not significant.