A cytokine receptor-targeting chimera toolbox for expanding extracellular targeted protein degradation.

ABSTRACT: Extracellular targeted protein degradation (eTPD) is an important new modality for manipulating the extracellular proteome. However, most eTPD receptors are expressed broadly or are restricted to the liver, limiting specific degradation in other tissues. Cytokine receptor-targeting chimeras (kineTACs) are genetically encoded bispecifics for eTPD that fuse a natural ligand like CXCL12 to an antibody, directing soluble or membrane proteins for lysosomal degradation using the widely expressed chemokine receptor CXCR7 (K. Pance et al., Nat. Biotechnol. 41, 273-281 (2023)]. Here, we dramatically expand the kineTAC toolbox by constructing 81 different kineTACs based on an unbiased list of cytokines, chemokines, and growth factors. Remarkably, 55 of these expressed at suitabl

SUBMITTER: Kumru K 

PROVIDER: S-EPMC12846780 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature