Piotr J. Kamola, Klio Maratou, Paul A

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Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs  Piotr J. Kamola, Klio Maratou, Paul A. Wilson, Kay Rush, Tanya Mullaney, Tom McKevitt, Paula Evans, Jim Ridings, Probash Chowdhury, Aude Roulois, Ann Fairchild, Sean McCawley, Karen Cartwright, Nigel J. Gooderham, Timothy W. Gant, Kitty Moores, Stephen A. Hughes, Mark R. Edbrooke, Kenneth Clark, Joel D. Parry  Molecular Therapy - Nucleic Acids  Volume 8, Pages 383-394 (September 2017) DOI: 10.1016/j.omtn.2017.07.003 Copyright © 2017 GSK R&D Terms and Conditions

Figure 1 Expression Profiles of OTEs, Indicated in Red, Compared to Transcripts Not Predicted to Interact with the ASO, Indicated in Blue OTEs were defined as genes with zero- to one-MM and zero- to two-MM alignments relative to a particular oligonucleotide, for 14- and 16-mer ASOs, respectively. The difference in profiles and their significance were calculated using the KS test and are shown in Table 4. The ASOs are coded to represent an arbitrary score for high (++), low (+), and no (-) evidence of hepatotoxicity. Molecular Therapy - Nucleic Acids 2017 8, 383-394DOI: (10.1016/j.omtn.2017.07.003) Copyright © 2017 GSK R&D Terms and Conditions

Figure 2 Correlation Matrix Showing Dependence between Hepatotoxicity Descriptors Pearson’s correlation coefficients are presented for KS-test values, average ALT/AST levels, liver weights, number of potent OTEs, hepatotoxicity scores, and number of activated genes annotated as involved in hepatocellular carcinoma for all ASOs used in acute studies 1 and 2 (excluding Sequence 1). Molecular Therapy - Nucleic Acids 2017 8, 383-394DOI: (10.1016/j.omtn.2017.07.003) Copyright © 2017 GSK R&D Terms and Conditions