Assay Development to Predict Toxicity of Antisense Oligonucleotide (ASO) Therapeutic Candidates for Rare Diseases

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

We have engaged in productive partnerships across various therapeutic areas in collaboration with NIH and external academic researchers and companies. The team has made significant progress in developing liver toxicity and neurotoxicity assays utilizing 2D and 3D organoid models. Liver toxicity assays involve measuring multiple cellular viability and functional indicators in 3D organoids and analyzing thousands of data points using statistical algorithms from tested ASOs. Neurotoxicity assay development has been completed using MEA and FLIPR assays to predict safe or toxic ASOs. So far, we have achieved high correlation in predicting the safety or toxicity of ASOs that were known through other methods to be safe or toxic. In vivo toxicity measurements were completed to generate supporting data for these predictive cell-based assays. We are collaborating with NCATS informatics scientists to validate the predictivity of the cell-based assays using an AI-powered algorithm to analyze the data from a set of benchmark ASOs. Manuscripts are in preparation.