For decades the pharmaceutical industry has synthesized millions of molecular entities in the pursuit of novel biological activities. These huge compound libraries have always been considered a treasure trove of potential new drugs for a plethora of new therapeutic targets. With the huge progress in laboratory automation and high-throughput technology over the last decade, library screening remains a key drug discovery strategy. The size of these libraries and their handling present however multiple challenges, starting from the synthesis and screening speed, storage space, and annotation required when working with Singleton compounds. A clever alternative finds inspiration from biology and leverages the DNA information storage power. This is known as DNA Encoded Libraries, or DELs. Dr. Katelyn Billings is a pioneer of this technology that offers a number of advantages, starting from the possibility of working on the nanoscale in as little as a few microliters to make and screen millions of molecules as a pool. In this episode we learn about how DELs work and discuss their advantages, challenges and the promise of combining data from DEL screens with machine learning to disrupt modern drug discovery.

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