title: Signal propagation in multi-layer DNAzyme cascades using structured chimeric substrates.
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.
authors.affiliation: Center for Biomedical Engineering, Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM 87131 (USA).
authors.forename: Carl W
authors.initials: CW
authors.lastname: Brown
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lakin
authors.forename: Eli K
authors.initials: EK
authors.lastname: Horwitz
authors.forename: M Leigh
authors.initials: ML
authors.lastname: Fanning
authors.forename: Hannah E
authors.initials: HE
authors.lastname: West
authors.forename: Darko
authors.initials: D
authors.lastname: Stefanovic
authors.forename: Steven W
authors.initials: SW
authors.lastname: Graves
mesh_terms: D015374:Biosensing Techniques; D021881:DNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009693:Nucleic Acid Hybridization; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D021881:DNA, Catalytic
keywords: DNA recognition; DNAzymes; regulatory networks; signaling cascades; strand displacement