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Updated: Feb 25, 2026
Efficient Sampling of Genetically Encoded Biosensor Design Space Enabled with a Design of Experiments and Automation Workflow
Published on: October 17, 2025
Design, preparation, and selection of DNA-encoded dynamic libraries
Gang Li1, Wenlu Zheng2, Zitian Chen3
1Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education , Beijing National Laboratory of Molecular Sciences (BNLMS) , College of Chemistry and Molecular Engineering , Peking University , Beijing , China 100871 .
Abstract:
We report a method for the preparation and selection of DNA-encoded dynamic libraries (DEDLs). The library is composed of two sets of DNA-linked small molecules that are under dynamic exchange through DNA hybridization. Addition of the protein target shifted the equilibrium, favouring the assembly of high affinity bivalent binders. Notably, we introduced a novel locking mechanism to stop the dynamic exchange and "freeze" the equilibrium, thereby enabling downstream hit isolation and decoding by PCR amplification and DNA sequencing. Our DEDL approach has circumvented the limitation of library size and realized the analysis and selection of large dynamic libraries. In addition, this method also eliminates the requirement for modified and immobilized target proteins.
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