Binding-Induced DNA Nanomachines Triggered by Proteins and Nucleic Acids

• Published in: Angewandte Chemie International Edition 2015-11, Vol.54 (48), p.14326-14330
• Main Authors: Zhang, Hongquan, Lai, Maode, Zuehlke, Albert, Peng, Hanyong, Li, Xing-Fang, Le, X. Chris
• Format: Article
• Language: English
• Subjects: Affinity; Arm; Assembly; Binding; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA assembly; DNA nanomachines; gold nanoparticles; Growth factors; Harnesses; Ligands; Nanoparticles; Nanotechnology; Nucleic acids; Nucleic Acids - chemistry; Oligonucleotides; Proteins; Proteins - chemistry; Smallpox; Streptavidin
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201506312

We introduce the concept and operation of a binding‐induced DNA nanomachine that can be activated by proteins and nucleic acids. This new type of nanomachine harnesses specific target binding to trigger assembly of separate DNA components that are otherwise unable to spontaneously assemble. Three‐dimensional DNA tracks of high density are constructed on gold nanoparticles functionalized with hundreds of single‐stranded oligonucleotides and tens of an affinity ligand. A DNA swing arm, free in solution, is linked to a second affinity ligand. Binding of a target molecule to the two ligands brings the swing arm to AuNP and initiates autonomous, stepwise movement of the swing arm around the AuNP surface. The movement of the swing arm, powered by enzymatic cleavage of conjugated oligonucleotides, cleaves hundreds of oligonucleotides in response to a single binding event. We demonstrate three nanomachines that are specifically activated by streptavidin, platelet‐derived growth factor, and the Smallpox gene. Substituting the ligands enables the nanomachine to respond to other molecules. The new nanomachines have several unique and advantageous features over DNA nanomachines that rely on DNA self‐assembly. Binding of a target molecule to two ligands brings the swing arm to the gold nanoparticle (AuNP) and initiates autonomous, stepwise movement of the swing arm along the three‐dimensional DNA tracks on the AuNP surface. The movement of the swing arm, powered by enzymatic cleavage of DNA anchorages, cleaves hundreds of oligonucleotides in response to a single binding event.