DEL Screening to Discover Small Molecule Ligands for RNA

RNA-targeted therapeutics are highly intriguing due to their unique physiological properties and novel modes of action in drug R&D. Developing methods to target RNA can lead to new therapeutic options, especially for conditions where RNA plays a pivotal role, such as genetic disorders, viral infections, and cancer. Over the past decade, discovering novel chemical matter has been a major bottleneck in RNA-targeted therapeutics development.

In our latest publication, WuXi Biology scientists introduced the “DEL Zipper”, a specialized DNA-encoded library (DEL) screening assay designed to discover small molecule ligands for diverse RNA targets. The DEL Zipper method significantly reduces single-stranded DNA-RNA region interaction signals during various RNA selections. By targeting G-quadruplex structures, we identified novel hits that interact with RNA targets, and validated these results through various binding assays.

“DEL Zipper” offers new tools and methods to explore RNA as a therapeutic target and expands the utility of DEL beyond proteins.

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