Hoffmann-la Roche Inc.

Roche Innovation Center Copenhagen A/s

F. Hoffmann-la Roche Ag

Adrian B Roth

Annie Moisan

Sabine Sewing

Marcel Gubler

Franziska Boess

Cristina Bertinetti-Lapatki

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.

Growing community of inventors

Riehen, Switzerland

Adrian B Roth