DNA-Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution.

DNA-encoded library (DEL) technologies are transforming the drug discovery process, enabling the identification of ligands at unprecedented speed and scale. DEL makes use of libraries that are orders of magnitude larger than traditional high throughput screens. While a DNA tag alludes to a genotype-phenotype connection that is exploitable for evolutionary cycles, most of the work in the field is performed with libraries where the tag serves as an amplifiable bar code but does not allow 'translation' into the synthetic product it is linked to. In this review, we cover technologies that enable the 'translation' of the genetic tag into synthetic molecules, both biochemically and chemically, and explore how it can be used to harness Darwinian evolutionary pressure.