title: Antibody-controlled actuation of DNA-based molecular circuits.
abstract: DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically. Detailed characterization of the ATSE reaction allowed the establishment of a comprehensive model that describes the kinetics and thermodynamics of ATSE as a function of toehold length, antibody-epitope affinity and concentration. ATSE enables the introduction of complex signal processing in antibody-based diagnostics, as demonstrated here by constructing molecular circuits for multiplex antibody detection, integration of multiple antibody inputs using logic gates and actuation of enzymes and DNAzymes for signal amplification.
authors.affiliation: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Engelen
authors.affiliation: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Lenny H H
authors.initials: LH
authors.lastname: Meijer
authors.affiliation: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: Somers
authors.affiliation: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Tom F A
authors.initials: TF
authors.lastname: de Greef
authors.affiliation: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Merkx
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D021881:DNA, Catalytic / Q000378:metabolism; D007700:Kinetics; D016018:Least-Squares Analysis; D008128:Logic; D008954:Models, Biological; D017711:Nonlinear Dynamics
chemical_list: D000906:Antibodies; D021881:DNA, Catalytic; D004247:DNA