Life › Biotech1 min read

FIND platform screens molecular modulators with DNA nanoswitches in vitro

Researchers combined DNA nanoswitch selection with sequencing to identify compounds that induce or enhance protein-protein interactions.

FIND platform screens molecular modulators with DNA nanoswitches in vitro
Photo: Authors of the study: Stefan A. Hoffmann James Diggans Douglas Densmore Junbi, Wikimedia Commons, CC BY 4.0 · License: CC BY 4.0

Researchers developed Functional Interaction–based Nanoswitch Discovery (FIND), an ultrahigh-throughput screening platform that identifies compounds modulating protein-protein interactions, as reported in Science doi.orgSciencedoi.orgOpen source ↗. The method combines DNA nanoswitch–based selection of nucleotide-encoded libraries with next-generation sequencing to directly detect multibody molecular interactions and ternary complex formation doi.orgSciencedoi.orgOpen source ↗.

The authors demonstrated the platform in vitro by screening for molecules that influence specific target proteins doi.orgSciencedoi.orgOpen source ↗. The team used FIND to discover nanobodies that stabilize the interaction between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) doi.orgSciencedoi.orgOpen source ↗. Additionally, the workflow identified peroxisome proliferator–activated receptor gamma agonists from a DNA-barcoded small-molecule library doi.orgSciencedoi.orgOpen source ↗.

Standard screening techniques often lack sufficient throughput or struggle to directly analyze multibody interactions doi.orgSciencedoi.orgOpen source ↗. According to the authors, the approach provides a rapid mechanism to discover molecular modulators that induce or increase targeted protein complexes doi.orgSciencedoi.orgOpen source ↗.

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