PANCS-Binders: a rapid, high-throughput binder discovery platform.

ABSTRACT: Proteins that selectively bind to a target of interest are foundational in research, diagnostics and therapeutics. Current approaches for discovering binders are laborious and time-consuming, taking months or more, and have a high failure rate. Here we establish phage-assisted noncontinuous selection of protein binders (PANCS-Binders), an in vivo selection platform that links the life cycle of M13 phage to target protein binding through proximity-dependent split RNA polymerase biosensors, allowing for comprehensive screening of whether a variant binds a target with high fidelity. We showcase PANCS-Binders by screening multiple protein libraries each against a panel of 95 separate targets, thereby individually assessing more than 10¹¹ protein-protein interaction pairs, in 2 days.

SUBMITTER: Styles MJ 

PROVIDER: S-EPMC12328212 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature