title: Designable DNA-binding domains enable construction of logic circuits in mammalian cells.
abstract: Electronic computer circuits consisting of a large number of connected logic gates of the same type, such as NOR, can be easily fabricated and can implement any logic function. In contrast, designed genetic circuits must employ orthogonal information mediators owing to free diffusion within the cell. Combinatorial diversity and orthogonality can be provided by designable DNA- binding domains. Here, we employed the transcription activator-like repressors to optimize the construction of orthogonal functionally complete NOR gates to construct logic circuits. We used transient transfection to implement all 16 two-input logic functions from combinations of the same type of NOR gates within mammalian cells. Additionally, we present a genetic logic circuit where one input is used to select between an AND and OR function to process the data input using the same circuit. This demonstrates the potential of designable modular transcription factors for the construction of complex biological information-processing devices.
authors.affiliation: 1] Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia. [2] EN-FIST Centre of Excellence, Ljubljana, Slovenia. [3].
authors.forename: Rok
authors.initials: R
authors.lastname: Gaber
authors.affiliation: 1] Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia. [2] EN-FIST Centre of Excellence, Ljubljana, Slovenia. [3].
authors.forename: Tina
authors.initials: T
authors.lastname: Lebar
authors.affiliation: 1] Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia. [2] EN-FIST Centre of Excellence, Ljubljana, Slovenia.
authors.forename: Andreja
authors.initials: A
authors.lastname: Majerle
authors.affiliation: Faculty of Computer and Information Science, University of Ljubljana, Slovenia.
authors.forename: Branko
authors.initials: B
authors.lastname: Šter
authors.affiliation: Faculty of Computer and Information Science, University of Ljubljana, Slovenia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Dobnikar
authors.affiliation: 1] Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia. [2] EN-FIST Centre of Excellence, Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Benčina
authors.affiliation: 1] Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia. [2] EN-FIST Centre of Excellence, Ljubljana, Slovenia.
authors.forename: Roman
authors.identifier: 0000000263375251
authors.initials: R
authors.lastname: Jerala
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D008128:Logic; D017434:Protein Structure, Tertiary; D058615:Synthetic Biology
chemical_list: D004247:DNA