Our Science
The development and progression of human diseases frequently involves complex aberrations in gene expression. At QUANTRO Therapeutics, we employ transformative technologies in molecular biology to herald a new era in the discovery of therapeutics that interfere with aberrant transcriptional programs.
Discovery Approach
At QUANTRO Therapeutics we strive to establish a novel class of effective anti-tumor therapeutics that interfere with disease-causing transcriptional programs in cancer. To achieve this, we are combining cutting-edge technologies in the area of functional genetics and comparative transcriptomics in an unprecedented experimental pipeline for the identification of new chemical entities (NCEs) in cell-based compound screens. Our prime focus is the discovery and development of drug candidates blocking the activity of oncogenic transcription factors, a class of particularly promising therapeutic targets that has so far remained largely unamenable to pharmacological intervention.
Key Technologies
Fingerprinting oncogenes by time-resolved transcriptomics
The unbiased detection and quantification of direct transcriptional effects has remained challenging due to the limited temporal resolution of conventional techniques for gene perturbation and transcriptional profiling. We are combining rapid protein depletion with time-resolved transcriptomics to derive and classify the transcriptional signatures of disease-causing transcription factors. By combining genome engineering with metabolic RNA sequencing and state-of-the-art bioinformatics we will establish the most advanced time-resolved transcriptomics pipeline to systematically unravel disease-causing transcriptional fingerprints in intact cells at unprecedented sensitivity, specificity and efficiency.
Next-generation cell-based compound screening
Traditional cell-based compound screens frequently fail to distinguish specific on-target perturbations from pleiotropic off-target effects. By developing scalable assays for massively parallel transcriptional fingerprinting, QUANTRO strives to transform the precision and scope of cell-based compound screens. A first focus is to employ this innovative approach to systematically match oncogenic transcriptional fingerprints to pharmacologic perturbations in order to identify and develop drug candidates that specifically interfere with disease-causing transcriptional programs in cancer and other diseases.
References
Herzog, V. et al. (2017). Thiol-linked alkylation of RNA to assess expression dynamics. Nature Methods, 14 (12), pp.1198-1204. https://doi.org/10.1038/nmeth.4435
Muhar, M. et al. (2018). SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis. Science, 360 (6390), pp.800-805. https://doi.org/10.1126/science.aao2793
Neumann T, et al. (2019). Quantification of experimentally induced nucleotide conversions in high-throughput sequencing datasets. BMC Bioinformatics, 20 (1), 258. https://doi.org/10.1186/s12859-019-2849-7
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