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. 2023 Apr 18;51(9):4126–4147. doi: 10.1093/nar/gkad268

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© The Author(s) 2023. 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-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Figure 10. — PN-based GalNAc-siRNA format translates to an additional liver target. (A) Schematic representation of siRNAs tested in the study. Dosing regimen for transgenic HSD17B13 mice, with dosing at day 0 (D0, green arrow) and mouse sacrifice and tissue evaluation at the indicated times (orange arrows) in weeks (W) post-dose. (B, C) HSD17B13 mRNA levels in liver of transgenic mice treated with the indicated siRNA 7-weeks post dose (B) or for the entire 14-week experiment (C). Data in B are presented as scatter plots with lines denoting mean mRNA levels. Data in C are presented as mean ± sem, n = 5. Stats: Two-way ANOVA with post-hoc comparison between HSD-1933 and HSD-1930 at each time point. ** P < 0.01, **** P < 0.0001. (D) Concentration of antisense strands in livers 2-, 7- or 14-weeks post-dose for the indicated treatment. Data are presented as mean ± sd, n ≥ 3. (E) Relative Ago2 loading for antisense strands in mouse livers over time with normalization to miR-122. Data are presented as mean ± sd, n = 5. Stats: Two-way ANOVA with post-hoc comparisons between HSD-1930 and HSD-1933 at each time point. (F) Fold-change Ago2 loading for HSD-1933 compared to HSD-1930 in mouse livers over time after normalization to miR-122. Data are presented as mean ± sd, n = 5.