Precision multidimensional assay for high-throughput microRNA drug discovery

Benjamin Haefliger, Laura Prochazka, Bartolomeo Angelici and Yaakov Benenson ()
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Benjamin Haefliger: Swiss Federal Institute of Technology (ETH Zürich)
Laura Prochazka: Swiss Federal Institute of Technology (ETH Zürich)
Bartolomeo Angelici: Swiss Federal Institute of Technology (ETH Zürich)
Yaakov Benenson: Swiss Federal Institute of Technology (ETH Zürich)

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract Development of drug discovery assays that combine high content with throughput is challenging. Information-processing gene networks can address this challenge by integrating multiple potential targets of drug candidates’ activities into a small number of informative readouts, reporting simultaneously on specific and non-specific effects. Here we show a family of networks implementing this concept in a cell-based drug discovery assay for miRNA drug targets. The networks comprise multiple modules reporting on specific effects towards an intended miRNA target, together with non-specific effects on gene expression, off-target miRNAs and RNA interference pathway. We validate the assays using known perturbations of on- and off-target miRNAs, and evaluate an ∼700 compound library in an automated screen with a follow-up on specific and non-specific hits. We further customize and validate assays for additional drug targets and non-specific inputs. Our study offers a novel framework for precision drug discovery assays applicable to diverse target families.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10709

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DOI: 10.1038/ncomms10709

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