Chronotoxici-plate Containing Rhythmic Liver Organoids for Drug Screening

ABSTRACT: The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many best-selling and WHO essential drugs, traditional approaches can’t satisfy the need of explore multi-timepoint drug administration strategies across a wide range of drugs. Here, we developed Chronotoxici-plate, a high-throughput automated rhythmic organoid tool for chronotherapy assessment. We identified Cry1 as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using Oxaliplatin as a representative drug, we demonstrated time-dependent variations in toxicity on the Chronotoxici-plate, highlighting the importance of considering time-dependent effects. Additionally, we observed improved development of rhythmic organoids, indicating a novel dimension in primary organoid culture. We successfully generated in vitro rhythmic primary organoids within four days, and enabled a preliminary assessment of chronotherapy's drug safety within seven days. This approach holds great promise for reducing drug side effects by optimizing administration timing and expanding the bank of available drugs.

ORGANISM(S): Mus Musculus

SUBMITTER: Shaohua Ma  

PROVIDER: PXD043268 | iProX | Sun Jun 25 00:00:00 BST 2023

REPOSITORIES: iProX