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. 2021 Jul 15;50(3):1221–1240. doi: 10.1093/nar/gkab544

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© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 4. — (A) In vitro evaluation of gene silencing in primary mouse hepatocytes incubated for 24 h with Ttr-targeted siRNAs under free-uptake conditions. a) Percent Ttr mRNA remaining quantified by RT-qPCR as a function of siRNA concentration for least (R/S-R, si7; S/S-R, si15) and most active (R/R-S, si5; S/R-S, si13) siRNAs relative to stereo-random parents (X/X-X, si1; XX/XX-XX, si19). b) Percent mRNA remaining as a function of siRNA concentration for siRNAs with a single isomer change at the 5′ end of the antisense strand (R/S-R, si7, R/R-R, si3; R/R-S, si5; R/S-S, si9; S/R-R, si11; S/S-R, si15; S/R-S, si13; S/S-S, si17) relative to the stereo-random parent (X/X-X, si1). c) Comparison of duplexes with a single isomer change at the 3′ end of the antisense strand (R/R-S, si5; R/R-R, si3; R/S-S, si9; R/S-R, si7; S/R-S, si13; S/R-R, si11; S/S-S, si17; S/S-R, si15) relative to the stereo-random parent (X/X-X, si1). d) Percent mRNA remaining as a function of siRNA concentration for siRNAs with a single isomer change at the 5′ end of the sense strand (R/R-R, si3; S/R-R, si11; R/R-S, si5; S/R-S, si13; R/S-R, si7; S/S-R, si15; R/S-S, si9; S/S-S, si17) relative to stereo-random parent (X/X-X, si1). (B) IC₅₀ values derived from above experiments for a) Ttr mRNA under transfection conditions, b) Ttr mRNA under free uptake conditions, c) C5 mRNA under transfection conditions and d) C5 mRNA under free uptake conditions. The star indicates values that could not be ascertained.