Antibody-controlled actuation of DNA-based molecular circuits

Wouter Engelen, Lenny H. H. Meijer, Bram Somers, Tom F. A. de Greef and Maarten Merkx ()
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Wouter Engelen: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Eindhoven University of Technology
Lenny H. H. Meijer: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Eindhoven University of Technology
Bram Somers: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Eindhoven University of Technology
Tom F. A. de Greef: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Eindhoven University of Technology
Maarten Merkx: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Eindhoven University of Technology

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14473

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