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Signal Propagation in Multi‐Layer DNAzyme Cascades Using Structured Chimeric Substrates
Author(s) -
Brown Carl W.,
Lakin Matthew R.,
Horwitz Eli K.,
Fanning M. Leigh,
West Hannah E.,
Stefanovic Darko,
Graves Steven W.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201402691
Subject(s) - deoxyribozyme , rational design , synthetic biology , nanotechnology , dna , cascade , chemistry , computer science , computational biology , materials science , biology , biochemistry , chromatography
Abstract Signal propagation through enzyme cascades is a critical component of information processing in cellular systems. Although such systems have potential as biomolecular computing tools, rational design of synthetic protein networks remains infeasible. DNA strands with catalytic activity (DNAzymes) are an attractive alternative, enabling rational cascade design through predictable base‐pair hybridization principles. Multi‐layered DNAzyme signaling and logic cascades are now reported. Signaling between DNAzymes was achieved using a structured chimeric substrate (SCS) that releases a downstream activator after cleavage by an upstream DNAzyme. The SCS can be activated by various upstream DNAzymes, can be coupled to DNA strand‐displacement devices, and is highly resistant to interference from background DNA. This work enables the rational design of synthetic DNAzyme regulatory networks, with potential applications in biomolecular computing, biodetection, and autonomous theranostics.