Applications and prospects of synthetic receptors for therapeutic protein delivery.

Synthetic receptors have gained prominence in synthetic biology due to their tunability, simplicity, versatility, and capacity for precise gene editing, which collectively enhance the temporal and spatial control of therapeutic protein delivery. Several types of synthetic receptors have been engineered to deliver specific therapeutic proteins, including G protein-coupled receptor (GPCR)-based receptor systems, modular extracellular sensor architecture (MESA), synthetic Notch (synNotch) receptor, and synthetic intramembrane proteolysis receptors (SNIPRs). These receptors have demonstrated therapeutic potential in targeting tumors, inflammatory immune diseases, central nervous system disorders, arthropathies, and viral infections by delivering specific proteins to diseased tissues. However, several challenges persist, including safety concerns, suboptimal delivery efficiency, and receptor design and optimization complexity. This review summarizes the current types, characteristics, and biomedical applications of synthetic receptors for therapeutic protein delivery, while also addressing their limitations and potential future directions.