Application of On-bead DEL Technology in Target Protein Degradation Phenotypic Screen

DNA-encoded library (DEL) technology has been recognized as a major screening method, offering unique advantages through its ability to provide vast chemical diversity and multiplexed affinity-based screening. Recently, solid-phase On-bead DEL, also known as one-bead-one-compound (OBOC), has been developed to expand DEL screening from affinity-based screening into functional screening. Previous studies have shown that by combining On-bead DEL with microfluidics technology, biochemical activity-based screening could be performed in picoliter-sized droplets, and assay-active compounds could be identified.

At DEL Symposium 2025 in Boston, WuXi Biology presented a poster showcasing the further expansion of On-bead DEL technology into cellular assay-based screening. The authors describe the development of in-house microfluidics chips, along with a high-speed droplet sorting system and a unique compound loading strategy. To test this cellular assay-based On-bead DEL system, a target protein degradation (TPD) cellular assay case study was performed. In this study, the authors show that cells could be cultured in droplets for 24 hours with maintained viability and target protein expression. Reference compound treatment revealed that positive compound-encapsulated droplets exhibited significant signal loss compared to negative control compound-encapsulated droplets.

Poster_2025 DEL Symposium_On-bead DEL TPD Screen

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