Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 28, Pages 7183-7187Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201402691
Keywords
DNA recognition; DNAzymes; regulatory networks; signaling cascades; strand displacement
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Funding
- National Science Foundation [1027877, 1028238, 1318833]
- INCBN IGERT [DGE-0549500]
- New Mexico Cancer Nanoscience and Microsystems Training Center (NIH/NCI) [5R25CA153825]
- Division of Computing and Communication Foundations
- Direct For Computer & Info Scie & Enginr [1318833] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1026592] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1027877] Funding Source: National Science Foundation
- Div Of Electrical, Commun & Cyber Sys
- Directorate For Engineering [1028238] Funding Source: National Science Foundation
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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 (DNA-zymes) 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.
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