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. 2022 Dec 19;4(12):1812–1829. doi: 10.1038/s42255-022-00681-y

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 9 — A.- Splice-switching oligonucleotide (SSO8.3) promotes skipping of Scarb1 exon 12 in primary hepatocytes as determined by semi-quantitative PCR analysis (n = 3-4). B.- Volcano-plot showing LC-MS lipidomic analysis of L^ΔRbfox2 hepatocytes treated with 100 nM SSO8.3 or Scr for 16 h (n = 5-6). C.- Metabolomics analysis showing levels of total ceramide, D.- PUFA/non-PUFA TG ratio, E.- total sphingomyelin, and F.- total triglycerides (n = 5-6). G-I.- Heatmap showing LC-MS metabolomic analysis of L^WT and L^ΔRbfox2 hepatocytes treated with SSO8.3 or Scr. Intensities were normalised to internal standard and total cell counts. J.- Western-blot showing SR-BI/II levels in the liver after SSO8.3 treatment (n = 2). K.- RT-qPCR expression analysis in liver of mice treated with SSO8.3 or Scr of potential off-targets genes such as Dscc1, (L.-) Kcnj16 and (M.-) Rab10. N.- Effect of SSO8.3 injection on circulating ALT and O.- AST levels. P.- Liver/body weight ratio upon SSO8.3 injection (n = 7-10). Results are represented as mean ± s.e.m. Statistical significance was determined by one-way ANOVA or two-sided unpaired t-test of biologically independent samples.

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