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Combinatorial drug discovery in nanoliter droplets [Engineering]

The conventional single-agent approach to therapeutics is challenged by the redundancy and feedback in biological networks. The use of multiple drugs in combination might improve desired functional outcomes while reducing toxicity and overcoming drug resistance. However, the complexity and resources required to test many combinations have slowed discovery efforts. Here, we introduce a screening platform that automatically constructs combinations of drugs from nanoliter-scale droplets, greatly simplifying screening logistics and reducing resource consumption. We applied our platform to discover drug pairs that act synergistically against the model pathogen Escherichia coli . Our platform can be further developed to support many types of phenotypic assays in a variety of disease models.

Authors:   Anthony Kulesa; Jared Kehe; Juan E. Hurtado; Prianca Tawde; Paul C. Blainey
Journal:   Proceedings of the National Academy of Sciences current issue
Volume:   115
edition:   26
Year:   2018
Pages:   6685
DOI:   10.1073/pnas.1802233115
Publication date:   26-Jun-2018
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