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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… Click to show full abstract
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.
Journal Title: Methods in molecular biology
Year Published: 2019
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