Engineering viral protease-operated nanobodies for programmable and orthogonal control of protein function

Precise control of protein function in living cells is essential for engineering programmable biological systems. Here the authors present VIPbodies, nanobodies engineered with self-cleaving viral proteases that convert protease inhibition into drug-dependent antigen recognition. This approach enables the creation of orthogonal control systems, where the activity of a protein is dependent on the presence of a specific drug. The use of viral proteases as a self-cleaving mechanism allows for the precise control of protein function, reducing the need for complex regulatory circuits. The authors demonstrate the potential of VIPbodies in a range of applications, including protein purification, cell signaling, and biosensing. The orthogonal control system presented by the authors has the potential to revolutionize the field of protein engineering, enabling the creation of complex biological systems with precise control over protein function. However, it is essential to note that the use of viral proteases and nanobodies in this context is for research-use only and should not be used for therapeutic or diagnostic applications without further testing and validation. The authors acknowledge that the use of viral proteases and nanobodies in this context may raise concerns regarding biosafety and biosecurity. Therefore, it is crucial to exercise caution and follow proper safety protocols when handling these reagents. The development of VIPbodies and their applications in protein engineering is an exciting area of research that holds great promise for advancing our understanding of protein function and control. Further studies are needed to fully explore the potential of this technology and to address any concerns regarding biosafety and biosecurity.