Activity of the 2′OMe-modified panels of (A) PLK1424 and (B) PLK773 siRNA. Unmodified PLK1424 or PLK773 siRNA was compared in the Hep3B cell viability assay with the 2′OMe-modified duplexes 1/A, 2/A, 1/B, 2/B, 1/C, and 2/C that comprise the respective 2′OMe sense/AS oligonucleotides (see Table 1). Data show mean viability of triplicate cultures relative to PBS-treated cells and represent 2 independent experiments using SNALP-formulated siRNAs. (C) Cytokine induction by unmodified and 2′OMe PLK1 siRNA in vitro. Murine Flt3L DCs were treated with 5 μg/ml (350 nM) unmodified PLK773 and PLK1424 siRNA duplexes and their constituent sense (S) or AS oligonucleotides or the 2′OMe siRNA duplexes PLK773-1/B (1/B) and PLK1424-2/A (2/A) formulated in SNALP. IFN-α and IL-6 were assayed in culture supernatants at 24 hours. Values represent mean + SD of 3 separate experiments conducted in triplicate cultures. (D and E) Activity of SNALP-formulated KSP2263 siRNA in murine Neuro2a cells. (D) Correlation between KSP mRNA silencing and cell viability relative to PBS control. KSP mRNA was determined by bDNA analysis at 24 hours. Duplicate plates were assessed for cell viability at 72 hours. (E) Activity screen comparing the unmodified KSP2263 siRNA to KSP2263-U/U (U/U), KSP2263-G/U (G/U), and KS2263-G/G (G/G) siRNA duplexes that comprise the respective sense/AS 2′OMe oligonucleotides (see Table 1). SNALP-formulated KSP2263 siRNA were tested in the Neuro2a cell viability assay. Data represent mean ± SD triplicate cultures, relative to PBS treatment.