Finally, tested the specificity of our tool by measuring its activity against a non-target protein. Then, we tested if a mutation-induced reduction in protease activity can be recovered by a VHH-directed increase in specificity. We first aimed to test if fusing a protease to a VHH increases the overall degradation rate of the VHH’s target as compared to the protease alone. Specifically, we wanted to limit degradation of all non-target proteins by reducing the intrinsic activity of a protease, then add a target-specific antibody in order to maintain an effective activity against one specific target protein. Our proof of concept aimed to demonstrate improved specificity of a protease by fusing it to a specific antibody.
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