Lipid-mediated intracellular delivery of recombinant bioPROTACs for the rapid degradation of undruggable proteins.

ABSTRACT: Recently, targeted degradation has emerged as a powerful therapeutic modality. Relying on "event-driven" pharmacology, proteolysis targeting chimeras (PROTACs) can degrade targets and are superior to conventional inhibitors against undruggable proteins. Unfortunately, PROTAC discovery is limited by warhead scarcity and laborious optimization campaigns. To address these shortcomings, analogous protein-based heterobifunctional degraders, known as bioPROTACs, have been developed. Compared to small-molecule PROTACs, bioPROTACs have higher success rates and are subject to fewer design constraints. However, the membrane impermeability of proteins severely restricts bioPROTAC deployment as a generalized therapeutic modality. Here, we present an engineered bioPROTAC template able to complex with c

SUBMITTER: Chan A 

PROVIDER: S-EPMC11237011 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature