Antisense oligonucleotides (ASOs) provide a powerful tool for drug development. To develop these therapies physiological models and approaches are needed to maximize clinical translation while mimizing the use of laboratory animals. Predicting acute side effects early in the drug development process saves time and resources by facilitating confident selection of candidate ASOs and increasing the success rate in preclinical and clinical stages.
In this study, we developed two robust assay modalities using two hiPSC-derived neuronal cell models to screen efficacy and neurotoxicity of ASOs. We have succesfully established a fully automated assay, including a highly robust calcium transient assay. With this we are able to determine dose dependent neurotoxity of ASOs and select fewer candidates to take forward for in vivo toxicity studies.