DNA nanomachines

Bath, Jonathan; Turberfield, Andrew J.

doi:10.1038/nnano.2007.104

Cited by 946 publications

(605 citation statements)

References 120 publications

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“…By taking advantage of the high versatility and designability of DNA chemistry [9][10][11][12][13][14][15][16][17][18][19] several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites.…”

Section: Introductionmentioning

confidence: 99%

Programmable pH-Triggered DNA Nanoswitches

2014

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ABSTRACT:Here we have rationally designed a tunable DNA-based nanoswitch whose closing/opening can be triggered over specific different pH windows. This nanoswitch forms an intramolecular triplex DNA structure through pH-sensitive parallel Hoogsteen interactions. We demonstrate that by simply changing the relative content of TAT/CGC triplets in the switch we can rationally tune its pH-dependence over more than 5 pH units. By using a combination of such nanowitches with different pH sensitivity, we also demonstrate how we can engineer a pH nanosensor that can precisely monitor pH variations over 5.5 units of pH. With their fast response time (<200 msec) and high reversibility, these pH-triggered nanoswitches appear particularly suitable for applications ranging from the real-time monitoring of pH changes in-vivo to the development of pH sensitive smart nanomaterial.Nature often employs finely pH-regulated biomolecules to modulate and tune a number of biological activities 1 ranging from enzyme catalysis 2 to protein folding 3 , membrane function 4 and apoptosis 5 . For these reasons, developing probes, switches or nanomaterials that are able to respond to specific pH changes should prove of utility for several applications in the fields of in-vivo imaging, clinical diagnostics, and drug-delivery [6][7][8] .By taking advantage of the high versatility and designability of DNA chemistry 9-19 several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites. These structures include I-motif [21][22][23]26,29,31 , intermolecular triplex DNA 25,28,32 , DNA tweezers 20 and, more recently, the Amotif 33 . Despite the promising and advantageous characteristics of some of these DNA-based nanomachines, which include fast response times and sustained efficiency over several cycles, a drawback inevitably affects their performances: they all respond (with an exception 33a ) over a fixed pH window that typically spans 1.5 to 2 pH units 26,34,33b . These nanomachines, therefore, cannot be adapted to provide a useful output outside these fixed pH-windows.Here we describe a method to rationally design and program pH-triggered DNA-based nanoswitches whose pH-dependence can be finely tuned and modulated over more than 5 units of pH. We created our switches by taking advantage of the wellcharacterized pH sensitivity of the parallel Hoogsteen (T,C)-motif in triplex DNA [34][35][36] . To do so we have designed a DNAbased triplex pH-triggered nanoswitch that consists in a double intramolecular hairpin stabilized with both Watson-Crick (W-C) and parallel Hoogsteen interactions (Fig. 1). More specifically, one hairpin of the triplex nanoswitch is formed by the W-C hybridization of two 10-base complementary portions separated by a 5 base loop. This duplex DNA is then able to form a triplex structure via the formation of a second hairpin through...

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Section: Introductionmentioning

confidence: 99%

Programmable pH-Triggered DNA Nanoswitches

2014

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“…5 Man-made devices mimicking their natural counterparts have been achieved in recent years. 6,7 Although these devices are advantageous in autonomous movement, the inelasticity of biomaterials in in vitro environments leads to limited lifetimes. 8 Nevertheless, the goal of developing self-regulating engines has inspired investigations into artificial micro-/nanoengines that operate on locally supplied chemical fuels (in contrast to biomaterials).…”

Section: Introductionmentioning

confidence: 99%

Hierarchical nanoporous microtubes for high-speed catalytic microengines

Liu

Huang

et al. 2014

NPG Asia Mater

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Powerful micro-/nano-motors with high speeds and large driving forces in fluids are of great importance in propelling micro-/ nanomachines for various tasks. Here, we achieved highly efficient catalytic locomotion in microtubular engines with hierarchical nanoporous walls. The sophisticated structures provide an enlarged surface area and improved reactant accessibility, which remarkably enhanced their catalytic activity toward H 2 O 2 decomposition, accelerating the microengine's speed. The fast catalytic locomotion of such hierarchical nanoporous microtubes makes them excellent candidates as efficient micro-machines for biomedical applications.

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“…Owing to the specifi city and predictability of Watson-Crick base pairing, engineerability and the ability to form a rich repertoire of unusual structures based on their sequence and external triggers, nucleic acids have proven to be a remarkably powerful scaff old to build a variety of programmable synthetic nanomachines 7 . Examples include DNA tweezers, walkers and DNA-hybridization powered molecular motors 8,9 . Despite the existence of several highly eff ective, naturally occurring nucleic acid-based devices in vivo and an array of complex, synthetic DNAbased molecular devices in vitro , the functional application of such rationally designed artifi cial DNA-based nanodevices within a living organism is yet to be achieved.…”

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An autonomous DNA nanomachine maps spatiotemporal pH changes in a multicellular living organism

et al. 2011

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Structural DNA nanotechnology seeks to build synthetic molecular machinery from DNA. DNA nanomachines are artifi cially designed assemblies that switch between defi ned conformations in response to an external cue. Though it has proved possible to create DNA machines and rudimentary walkers, the function of such autonomous DNA-based molecular devices has not yet been achieved inside living organisms. Here we demonstrate the operation of a pH-triggered DNA nanomachine inside the nematode Caenorhabditis elegans . The nanomachine uses fl uorescence resonance energy transfer to effectively map spatiotemporal pH changes associated with endocytosis in wild type as well as mutant worms, demonstrating autonomous function within the organismal milieu in a variety of genetic backgrounds. From this fi rst demonstration of the independent functionality of a DNA nanomachine in vivo , we observe that rationally designed DNA-based molecular devices retain their in vitro functionality with quantitative precision. This positions DNA nanodevices as exciting and powerful tools to interrogate complex biological phenomena.

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DNA nanomachines

Cited by 946 publications

References 120 publications

Programmable pH-Triggered DNA Nanoswitches

Programmable pH-Triggered DNA Nanoswitches

Hierarchical nanoporous microtubes for high-speed catalytic microengines

An autonomous DNA nanomachine maps spatiotemporal pH changes in a multicellular living organism

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