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. 2014 Nov 18;3(11):e210. doi: 10.1038/mtna.2014.61

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Copyright © 2014 American Society of Gene & Cell Therapy

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Higher polyethylene glycol (PEG) density reduces LNP-mediated immunostimulation in vitro. Human plasma cytokine profile after in vitro incubation of whole blood with 300 nmol/l siRNA formulated in lipid nanoparticles (LNP)1.5, LNP5, or LNP10 for 24 hours. A total of 13 cytokines were analyzed using blood from multiple donors (n = 4). Two-way analysis of variance examined the effect of treatment and analyte; Tukey's honestly significant difference pairwise comparisons showed significant cytokine elevations for LNP1.5 (P < 0.0001) and for LNP5 (P = 0.02) when compared to the medium alone control. In addition, cytokine levels were significantly higher for LNP1.5 compared to LNP10 (P = 0.002). The six individual analytes that best illustrate this trend are shown below (mean ± SEM for four blood donors). The other cytokines that were evaluated but showed either overall low expression or minor changes upon treatment were IL-1β, IL-10, IL-12, G-CSF, IFN-γ, MIP-1α, TNFα (data not shown).