DNA-based assembly lines and nanofactories

Simmel, Friedrich C.

doi:10.1016/j.copbio.2011.12.024

Cited by 90 publications

(69 citation statements)

References 46 publications

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“…As the presence of such anti-PAD4 antibodies has been shown to enhance the enzymatic activity of PAD4 in an extracellular environment by reducing the calcium requirement [33], their combination with NETs-associated PAD4 could lead to prodigious quantities of citrullinated autoantigens. In addition, the extracellular presence of PAD4 on NETs may further promote the prodigious generation of citrullinated antigens, because molecular structures involving the attachment of enzymes to DNA lattices have been shown to increase their catalytic activity enormously, and thereby form the basis of nano-machines or nano-factories, generating such autoantigens [34]. …”

Section: Discussionmentioning

confidence: 99%

Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility

et al. 2014

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IntroductionNeutrophil extracellular traps (NETs) have recently been implicated in a number of autoimmune conditions, including rheumatoid arthritis (RA). We examined the underlying signaling pathways triggering enhanced NETosis in RA and ascertained whether the products of NETosis had diagnostic implications or usefulness.MethodsNeutrophils were isolated from RA patients with active disease and from controls. Spontaneous NET formation from RA and control neutrophils was assessed in vitro with microscopy and enzyme-linked immunosorbent assay (ELISA) for NETosis-derived products. The analysis of the signal-transduction cascade included reactive oxygen species (ROS) production, myeloperoxidase (MPO), neutrophil elastase (NE), peptidyl arginine deiminase 4 (PAD4), and citrullinated histone 3 (citH3). NET formation was studied in response to serum and synovial fluid and immunoglobulin G (IgG) depleted and reconstituted serum. Serum was analyzed for NETosis-derived products, for which receiver operator characteristic (ROC) curves were calculated.ResultsNeutrophils from RA cases exhibited increased spontaneous NET formation in vitro, associated with elevated ROS production, enhanced NE and MPO expression, nuclear translocation of PAD4, PAD4-mediated citrullination of H3, and altered nuclear morphology. NET formation in both anti-citrullinated peptide antibody (ACPA)-positive and -negative RA was abolished by IgG depletion, but restored only with ACPA-positive IgG. NETosis-derived products in RA serum demonstrated diagnostic potential, the ROC area under the curve for cell-free nucleosomes being >97%, with a sensitivity of 91% and a specificity of 92%. No significant difference was observed between ACPA-positive and -negative cases.ConclusionsSignaling elements associated with the extrusion of NETs are significantly enhanced to promote NETosis in RA compared with healthy controls. NETosis depended on the presence of ACPA in ACPA-positive RA serum. The quantitation of NETosis-derived products, such as cell-free nucleosomes in serum, may be a useful complementary tool to discriminate between healthy controls and RA cases.

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Section: Discussionmentioning

confidence: 99%

Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility

et al. 2014

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“…These molecular-scale platforms could help us to construct entire "nanofactories" with fully tailored assembly lines [52]. Fascinating examples of nanoscale engineering include the possibility to organize intracellular reactions using RNA-scaffolds [53] and activate enzyme cascade reactions with DNA-based nanoassemblies [54].…”

Section: Smart Dna Nanodevices and Molecular Platformsmentioning

confidence: 99%

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices

Linko

Ora

Kostiainen

2015

Trends in Biotechnology

227

166

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Emerging DNA nanotechnologyThe field of structural DNA nanotechnology started around 30 years ago when Ned Seeman performed pioneering research with DNA junctions and lattices [1]. To date, a cornucopia of different DNA nanostructures and shapes based on WatsonCrick basepairing [2] have been designed and demonstrated, and the whole research area has enjoyed a rapid progress especially during the past decade [3]. The key player in the fast development of DNA nanotechnology has been the invention of DNA origami in 2006 [4]. The DNA origami method is based on folding a long single-stranded "DNA scaffold strand" into a customized shape with a set of short synthetic staple strands. The robustness of the technique has made it widely accessible.Since then, the method has been generalized to 3D-fabrication [5][6][7][8][9][10], and it enables shapes with custom curvatures, twists and bends [11,12]. Very recently, techniques for modular scaffold-free fabrication [13,14], 3D meshing and wireframe-based approaches [15][16][17], as well as shape-complementarity-based construction [18] of DNA objects have been introduced. In addition, powerful computational tools for designing and analyzing DNA nanostructures have been developed [19][20][21], which appreciably help researchers to create their own DNA nanoarchitectures for any conceivable application. Table 1 lists and 2 describes the novel design strategies that can be used for fabricating diverse DNA origami nanostructures and other complex DNA-based shapes for various nanotechnological purposes.The platonic DNA nanostructures and DNA origamis are by all means remarkably impressive examples of precise engineering and constructing at the nanoscale. However, the attractiveness of the origami method lies in the fact that one can add any desired functionality to the tailored DNA shapes by assembling other biomolecules and molecular components to them with nanometer precision. Importantly, DNA is inherently biocompatible, and its stability can be further tuned by the optional functionalization [20,[22][23][24]. Aforementioned superior features can be eventually exploited in designing artificial DNA-based biomachinery, such as nucleic acid devices [25] and protein-DNA hybrid structures [26] for nanomedicine and biosensing. In this focused review, we discuss the recent progress of the nanomedical applications of self-assembled DNA systems; especially the drug delivery vehicles and nanomachines based on the DNA origami technique. Towards DNA-based drug delivery vehicles and advanced therapeuticsThe tremendous self-assembly properties of DNA can be exploited in creating various programmable shapes and larger assemblies for cellular delivery for e.g. cancer and enzyme replacement therapy. The very first DNA origami nano-objects proposed to work as molecular containers for drug delivery applications were single-layer origamis, which were further assembled into 3D shapes -a tetrahedron [5] or hollow cubes [6,7] (Fig. 1A). Since then, cellular uptake for various DNA structures (based o...

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“…In many cases, compartmentalization could be used to efficiently separate and arrange simultaneous reactions and reaction compounds similar to complex natural systems [41]. Moreover, enzyme reactors can be equally utilized to study enzyme functions and reaction pathways [42]. In this section, recent examples of using DNA nanostructures to build (static) nanoreactors for biosensing and molecular-scale diagnostics are discussed (see also Table 1).…”

Section: Enzyme Reactors and Cascadesmentioning

confidence: 99%

DNA-Based Enzyme Reactors and Systems

et al. 2016

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During recent years, the possibility to create custom biocompatible nanoshapes using DNA as a building material has rapidly emerged. Further, these rationally designed DNA structures could be exploited in positioning pivotal molecules, such as enzymes, with nanometer-level precision. This feature could be used in the fabrication of artificial biochemical machinery that is able to mimic the complex reactions found in living cells. Currently, DNA-enzyme hybrids can be used to control (multi-enzyme) cascade reactions and to regulate the enzyme functions and the reaction pathways. Moreover, sophisticated DNA structures can be utilized in encapsulating active enzymes and delivering the molecular cargo into cells. In this review, we focus on the latest enzyme systems based on novel DNA nanostructures: enzyme reactors, regulatory devices and carriers that can find uses in various biotechnological and nanomedical applications.

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DNA-based assembly lines and nanofactories

Cited by 90 publications

References 46 publications

Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility

Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices

DNA-Based Enzyme Reactors and Systems

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