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2017 ; 8
(ä): 14473
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Antibody-controlled actuation of DNA-based molecular circuits
#MMPMID28211541
Engelen W
; Meijer LH
; Somers B
; de Greef TF
; Merkx M
Nat Commun
2017[Feb]; 8
(ä): 14473
PMID28211541
show ga
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.