Target discovery is the first key step in the pharmaceutical R&D process. It both entails the identification of novel targets (target identification) and activities to reduce the subsequent failure from incorrect biological hypotheses through early validation (target validation).
There are various techniques that can be applied to identify and validate the target. Roughly, they can be grouped into two broad target discovery strategies, i.e. the 'molecular' and 'systems' approach. In practice, however, both are used in varying proportions in different therapeutic areas.
The 'molecular' approach uses techniques such as genomics, proteomics, genetic association and reverse genetics, whereas the so-called 'systems' approach, not to be confused with ‘systems biology’, uses clinical and in vivo studies to identify potential new targets. During validation, modulation of gene expression and/or protein function in both cell and animal models is used to confirm the role of the target prior to passing on to the next drug discovery stage, i.e. lead finding. However, additional validation of the target will extend beyond the start of the lead finding process and often continues into the early drug development stages.
Prof Mihai Netea and his team at the Radboudumc developed new in vitro assays that were used to study and establish the phenomenon of Trained Immunity. Through extensive use of genomic screening clinical samples and subsequent in vitro as well as in vivo validation several novel epigenetic targets were identified that play a critical role in (controlling) trained immunity.