DNA-encoded library use in living cells for drug discovery

In this episode of Speaking of Mol Bio, host Steve Lewis speaks with Dr. Leif Larsen, Director of Biology at Vipergen, about the power of DNA-encoded libraries (DELs) in modern drug discovery. DEL technology enables researchers to screen extremely large chemical libraries by attaching a unique DNA barcode to each compound, allowing millions, or even hundreds of millions, of compounds to be analyzed simultaneously through sequencing.

Larsen explains how Vipergen’s platform flips traditional screening methods by storing massive compound libraries in a single tube and identifying binding interactions through DNA sequencing. He also describes their proprietary Binder Trap Enrichment (BTE) method, which links DNA barcodes when compounds successfully bind their protein targets. One of the company’s most innovative advances is performing DEL screening inside living Xenopus oocytes. By expressing target proteins in these large cells and microinjecting DNA-encoded libraries, researchers can evaluate binding events in a physiologically relevant environment.

The discussion also explores how this technology accelerates early drug discovery timelines and enables screening of difficult targets such as transcription factors and membrane proteins. Larsen closes by highlighting emerging areas such as PROTAC-based targeted protein degradation and how DEL screening can help identify molecules suitable for these next-generation therapeutic strategies.

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