Here, we develop a highly multiplexed, quantitative, ChIP-Seq technology (hmqChIP-Seq) for commercial exploitation in high-throughput profiling of epigenetic drug on- and off-target effects. Screening efficacy and toxicology of dr...
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Información proyecto hmqChIP
Duración del proyecto: 18 meses
Fecha Inicio: 2020-12-18
Fecha Fin: 2022-06-30
Líder del proyecto
KAROLINSKA INSTITUTET
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
150K€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
Here, we develop a highly multiplexed, quantitative, ChIP-Seq technology (hmqChIP-Seq) for commercial exploitation in high-throughput profiling of epigenetic drug on- and off-target effects. Screening efficacy and toxicology of drug candidates in early stages of development has been recognized to be an essential part of drug screening. 90% of all Phase I drug candidates do not reach FDA approval and it is estimated that a quarter of failures relates to unexpected toxicity in humans. This is stunning given that all Phase I drugs have undergone animal-heavy battery of toxicologic tests and showcases the importance of expanding the screening capabilities for drug efficacy and toxicology in human cell-based assays, be it standard culture, organoids or engineered tissues. We believe that the interaction of drugs with the epigenome is an understudied/undervalued area of pre-clinical testing and epigenetic drug profiling will be key in predicting long term outcome in humans. With hmqChIP-Seq, 96 or more drug conditions can be screened against 24 or more epigenomic markers, such as histone or DNA post-translational modifications using specific antibodies and next-generation sequencing read-out. The method development aims to reduce the necessary input material to 1000 cells per condition, allowing it to be placed downstream of typical high-throughput cell-based drug screening assay in a variety of relevant human cell models, such as induced pluripotent stem cells, engineered tissues, organoids. The technology provides a framework for high-throughput, low cost, elucidation of short and long term action and toxicology of epigenetic drugs, or any drug candidate that could affect epigenetic markers.