Harnessing Viral Proteases for Cellular and Molecular Engineering

Viral proteases (VIPs) are naturally evolved enzymes that cleave viral polyproteins into functional proteins with remarkable specificity, orthogonality, and minimal cytotoxicity in mammalian cells. These unique properties have positioned VIPs as indispensable tools in synthetic biology, enabling precise and programmable control of protein activity. By recognizing defined cleavage sites, VIP‐based systems can facilitate targeted protein release or degradation, driving innovations in the design of genetically encoded sensors and actuators. Engineered VIP systems have been applied to record dynamic cellular events, modulate signaling pathways, and regulate gene expression with high precision. Their versatility and reliability have unlocked transformative applications across diverse fields, including neural circuit mapping, high‐throughput drug discovery, and targeted cancer therapies. The exceptional precision, robustness, and safety of VIPs continue to advance their role as cornerstone technologies in synthetic biology, thereby empowering the creation of next‐generation molecular tools and therapeutic innovation.