Hoffmann-La Roche Inc.

Roche Innovation Center Copenhagen A/s

F. Hoffmann-La Roche Ag

Annie Moisan

Marcel Gubler

Sabine Sewing

Adrian B Roth

Henrik Frydenlund Hansen

Troels Koch

Jacob Ravn

Christoph Rosenbohm

Peter Hagedorn

Nanna Albaek

Cristina Bertinetti-Lapatki

Franziska Boess

Adrian Roth

The invention relates to methods for predicting the in vivo nephrotoxicity of a nucleic acid molecule, in particular a nucleic acid molecule such as a siRNA or an antisense oligonucleotide using an in vitro cell based assay measuring the levels of EGFR as toxicity biomarker, potentially in combination with other biomarkers like ATP and KIM-1.

In vitro nephrotoxicity screening assay

The invention relates to methods for predicting the in vivo nephrotoxicity of a drug substance, in particular a nucleic acid molecule such as a siRNA or an antisense oligonucleotide using an in vitro cell based assay measuring the levels of extracellular EGF as toxicity biomarker, potentially in combination with other biomarkers like ATP and KIM-1.

The invention relates to methods for predicting the in vivo toxicity of oligonucleotides, such as antisense oligonucleotides using in vitro cell based assays based on gymnotically administering oligonucleotides to primary mammalian hepatocytes and subsequently measuring the levels of toxicity biomarkers such as the release of LDH into the cell culture media and/or intracellular ATP.

In vitro toxicity screening assay

The invention relates to a method of identifying stereodefined phosphorothioate oligonucleotide variants with reduced toxicity by creating and screening libraries of stereodefined chiral phosphorothioate variants for compounds with reduced toxicity, either in vitro or in vivo.

Chiral library screen

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Basel, Switzerland

Annie Moisan