Antibody Activation using DNA‐Based Logic Gates

Janssen, Bmg Brian; Rosmalen, M Martijn van; Beek, L Lotte van; Merkx, Maarten

doi:10.1002/anie.201410779

Cited by 75 publications

(67 citation statements)

References 37 publications

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“…[70][71][72][73] The recognition of targets by DNA or RNA devices that induce sophisticated secondary functions based on Boolean logic-gated mechanisms are particularly impressive, utilizing conjunction (AND), disjunction (OR), or negation (NOT) operations. 74 Logic-gate operations performed by DNA were demonstrated by Adleman and Lipton two decades ago, but DNA-based computing remains underdeveloped due to challenges associated with scale-up and slow reaction kinetics. 75,76 Church and coworkers recently designed a DNA nanorobot composed of over 200 unique oligonucleotides and capable of delivering payloads such as antibody fragments or nanoparticles to cells by incorporating an AND gate based on two locking aptamer-complement duplexes ( Figure 5).…”

Section: Molecular Switches Rotors and Motorsmentioning

confidence: 99%

Controlling Motion at the Nanoscale: Rise of the Molecular Machines

et al. 2015

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As our understanding and control of intra- and intermolecular interactions evolve, ever more complex molecular systems are synthesized and assembled that are capable of performing work or completing sophisticated tasks at the molecular scale. Commonly referred to as molecular machines, these dynamic systems comprise an astonishingly diverse class of motifs and are designed to respond to a plethora of actuation stimuli. In this Review, we outline the conditions that distinguish simple switches and rotors from machines and draw from a variety of fields to highlight some of the most exciting recent examples of opportunities for driven molecular mechanics. Emphasis is placed on the need for controllable and hierarchical assembly of these molecular components to display measurable effects at the micro-, meso-, and macroscales. As in Nature, this strategy will lead to dramatic amplification of the work performed via the collective action of many machines organized in linear chains, on functionalized surfaces, or in three-dimensional assemblies.

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Section: Molecular Switches Rotors and Motorsmentioning

confidence: 99%

Controlling Motion at the Nanoscale: Rise of the Molecular Machines

et al. 2015

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“…Owing to their versatility and modular nature, our sensors can be easily converted into molecular AND logic gates, [25] which signal the concomitant presence of two different macromolecular targets. We therefore fabricated a single sensor presenting both Dig and DNP ( Figure 5, top).…”

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confidence: 99%

A Modular, DNA‐Based Beacon for Single‐Step Fluorescence Detection of Antibodies and Other Proteins

et al. 2015

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A versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins has been developed. This system is based on a conformationswitching stem-loop DNA scaffold that presents a smallmolecule, polypeptide, or nucleic-acid recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair. The sensors respond rapidly (< 10 min) and selectively, enabling the facile detection of specific proteins even in complex samples, such as blood serum. The versatility of the platform was demonstrated by detecting five bivalent proteins (four antibodies and the chemokine platelet-derived growth factor) and two monovalent proteins (a Fab fragment and the transcription factor TBP) with low nanomolar detection limits and no detectable cross-reactivity.Recent years have seen a significant increase in the number of well-characterized biomarkers, proteins present in the blood or on cells that are diagnostic of disease. [1][2][3] Unfortunately, however, current methods for the detection of such markers are based on either multistep, wash-, or reagentintensive processes and require sophisticated, laboratorybased measurements (e.g., ELISA or Western blot assays) or are at best only semi-quantitative (e.g., immunochemical dipsticks).[4-6] These drawbacks limit the accessibility of quantitative molecular diagnostics, resulting in delayed treatment, reduced compliance, and poorer outcomes. [1,2, 7] In contrast to the cumbersome, multistep nature of current detection schemes, however, biomolecular receptors present in organisms respond to changes in the concentration of their targets in a quantitative fashion and without needing the addition of reagents or wash steps. [8,9] Indeed, these receptors detect thousands of distinct molecules in real time even in the complex in vivo environment.[10] Building artificial biosystems of similar simplicity, convenience, and selectivity represents a major bioengineering goal.One of the strategies used by naturally occurring "sensors" [11] is based on conformational switching in which a receptor undergoes a large-scale, binding-induced conformational change in the presence of its target. [8,9] As their signaling is linked to a specific, binding-induced event, such "switches" are highly selective and enable detection even in highly complex sample matrices.[10] Moreover, such conformational changes can also be harnessed in artificial systems, where they can be used to generate an optical or electrochemical signal without the addition of exogenous reagents or coupling to exogenous biochemical reactions. [12,13] Motivated by these considerations, we have developed a single-step method for the quantitative detection of specific proteins that is rapid, inexpensive, and highly selective. We drew inspiration from DNA molecular beacons, which are synthetic nucleic acid switches for t...

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“…A TnT-immunosensor with a rapid response and low detection limit would be highly beneficial2. There would be added benefit in having a reversible immunosensor, and various approaches to achieve this have been described3456789101112. However, these biosensors suffered from perturbations resulting from the use of pH or ionic shifts and co-existing molecules in biological fluids.…”

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confidence: 99%

On/off-switchable LSPR nano-immunoassay for troponin-T

Ashaduzzaman

Deshpande

Murugan

et al. 2017

Sci Rep

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Regeneration of immunosensors is a longstanding challenge. We have developed a re-usable troponin-T (TnT) immunoassay based on localised surface plasmon resonance (LSPR) at gold nanorods (GNR). Thermosensitive poly(N-isopropylacrylamide) (PNIPAAM) was functionalised with anti-TnT to control the affinity interaction with TnT. The LSPR was extremely sensitive to the dielectric constant of the surrounding medium as modulated by antigen binding after 20 min incubation at 37 °C. Computational modelling incorporating molecular docking, molecular dynamics and free energy calculations was used to elucidate the interactions between the various subsystems namely, IgG-antibody (c.f., anti-TnT), PNIPAAM and/or TnT. This study demonstrates a remarkable temperature dependent immuno-interaction due to changes in the PNIPAAM secondary structures, i.e., globular and coil, at above or below the lower critical solution temperature (LCST). A series of concentrations of TnT were measured by correlating the λLSPR shift with relative changes in extinction intensity at the distinct plasmonic maximum (i.e., 832 nm). The magnitude of the red shift in λLSPR was nearly linear with increasing concentration of TnT, over the range 7.6 × 10−15 to 9.1 × 10−4 g/mL. The LSPR based nano-immunoassay could be simply regenerated by switching the polymer conformation and creating a gradient of microenvironments between the two states with a modest change in temperature.

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Antibody Activation using DNA‐Based Logic Gates

Cited by 75 publications

References 37 publications

Controlling Motion at the Nanoscale: Rise of the Molecular Machines

Controlling Motion at the Nanoscale: Rise of the Molecular Machines

A Modular, DNA‐Based Beacon for Single‐Step Fluorescence Detection of Antibodies and Other Proteins

On/off-switchable LSPR nano-immunoassay for troponin-T

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