Creation of a gated antibody as a conditionally functional synthetic protein.

Abstract

The ability to conditionally direct antibodies is a potentially powerful application for Synthetic Biology in Medicine. Here we show that control of antibody binding through site-specific, chemical phosphorylation of a recognition domain creates a 'gated' antibody (Ab). This displays a crude Boolean logic where binding is induced in an enzyme-AND-antigen dependent manner. This 'AND-Ab' is therefore active only in the presence of two biomarker inputs: the simultaneous expression of a (cell surface) antigen and secreted enzyme to generate function in vitro, on cells and in mammalian tissue. Such gated Abs, either alone or in combination, could allow the application of logic strategies to enhance precision in biological interrogation, modulation and in therapy.