Within mammalian systems, there is a great opportunity to use synthetic genetic pathways to improve drug discovery based on phenotypes, to map the molecular origins of disease, and to improve therapies in complex cellular systems. While drug discovery relies on high-level marker staining and imaging in cellular assays, synthetic genetic pathways increase the potential for accuracy and speed. Here, we provide information on how circuits can improve the speed and accuracy of drug discovery, increase the efficiency of successful screening, capture disease-relevant dynamics in cellular assays, and simplify the validation and measurements of organoids and systems. MPS). By detecting cellular events and conditions at different lengths and time scales, circuits are changing the way we decipher the causal relationship between molecular events and phenotypes to improve the selectivity and sensitivity of cellular assays.
Improving phenotypic drug discovery with synthetic biology
New drug development requires the identification and optimization of functional molecules that are often performed sequentially through high-throughput screening, event validation, event extension, and preclinical disease modeling. Target-based drug discovery (TDD) programs aim to identify drug candidates that modulate a defined biological target believed to play a causal role in the onset or maintenance of disease. TDD programs provide precision by directly detecting the effectiveness of drug candidates using purified molecular targets. In contrast, phenotypic drug discovery (PDD) programs aim to identify drug candidates that modulate a physiologically relevant biological system or cell signaling pathway and pursue drug efficacy using cell-based assays.