In Vitro Assessment of the Hepatotoxicity Potential of Therapeutic Oligonucleotides

  • Sabine SewingEmail author
  • Tanja Minz
  • Franziska Boess
Part of the Methods in Molecular Biology book series (MIMB, volume 2036)


The mechanisms of antisense oligonucleotide-induced liver toxicity are still poorly understood. Assessment of the hepatic safety profile is currently mostly investigated directly in rodent studies. A predictive preclinical in vitro model that is capturing liver liabilities of antisense oligonucleotides can be of great help to be used as a first filter in the screening process of therapeutic oligonucleotides. We describe here an in vitro cytotoxicity assay using freshly isolated mouse hepatocytes or cryopreserved human hepatocytes that recapitulates the hepatotoxic profile of antisense oligonucleotides previously observed in rodents and can be used for the prioritization of molecules prior to in vivo testing.

Key words

Antisense oligonucleotide In vitro hepatotoxicity Liver perfusion Cytotoxicity Hepatocytes 3R 



We thank E. Durr and N. Schaub for their excellent support.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Roche Pharma Research and Early Development, Pharmaceutical Sciences (PS)Roche Innovation Center BaselBaselSwitzerland

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