Low-leakage cellular biosensor system

Abstract

The present invention is directed to a cellular biosensor system comprising (A) a repressor module comprising one or more genes, which in their cumulative gene action exert repressing and/or inhibitory effect(s) on (B), an output module comprising at least one gene comprising at least one output sequence generating one or more output signals (i) in the absence of repressing and/or inhibitory effect(s) of the repressor module (A) and (ii) in the presence of at least one recombinase expressed by (C), a recombinase module comprising at least one gene comprising at least one sequence encoding a site-specific recombinase that enables gene rearrangement in the output module resulting in one or more output signals in the absence of repressing and/or inhibitory effect(s) of the repressor module, wherein the repressing and/or inhibitory effects of the repressor module are controlled by one or more inputs that negatively affect the repressing and/or inhibitory effects of the repressor module (A). In addition, the present invention relates a biosensor network comprising the cellular biosensor system of the present invention and their uses in the diagnosis of a disease, for drug discovery, for biomanufacturing methods, for producing a transgenic animal, and for methods for the identification or classification of a cell status.