Molecular Interaction Analysis
Unrivaled Information Content
- Binding Kinetics
- Binding Affinity
- Protein Diameter
- Conformational Change
- Nuclease & Polymerase Activity
- Bispecific Binders & Avidity
- Melting & Thermodynamics
- Multimers & Aggregation
Spot our Highlights & News
Using the switchSENSE® technology, scientists in the IMED Biotech Unit at AstraZeneca have developed a novel “guide” molecule that is capable of directing the Cas9 nuclease to sites of precise genome editing. In the recent issue of Nature Communications, the authors describe how the guide molecule which, until now has been based on an RNA backbone, can in fact be made from a hybrid molecule incorporating DNA nucleotides.
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The CRISPR–Cas9 RNA-guided endonuclease system allows precise and efficient modification of complex genomes and is continuously developed to enhance specificity, alter targeting and add new functional moieties. However, one area yet to be explored is the base chemistry of the associated RNA molecules. Here we show the design and optimisation of hybrid DNA–RNA CRISPR and tracr molecules based on structure-guided approaches. Through careful mapping of the ribose requirements of Cas9, we develop hybrid versions possessing minimal RNA residues, which are sufficient to direct specific nuclease activity in vitro and in vivo with reduced off-target activity. We identify critical regions within these molecules that require ribose nucleotides and show a direct correlation between binding affinity/stability and cellular activity. This is the first demonstration of a non-RNA-guided Cas9 endonuclease and first step towards eliminating the ribose dependency of Cas9 to develop a XNA-programmable endonuclease.
More (nano) leverage!
In a recent publication in the Journal of the American Chemical Society, researchers from Dynamic Biosensors and the Kurt-Schwabe-Institut Meinsberg have demonstrated the persistent electrical actuation of a large DNA-origami nanostructure on a gold microelectrode. The 100 nm long rigid rod was composed of six parallel, intertwined DNA helices and could be tethered to a standard multi-purpose chip by modular DNA adaptors.
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“While our standard DNA nanolevers are perfectly suited to analyze proteins up to 20 nm in diameter, this novel mega-nanolever will enable us to actuate and probe large protein complexes, multi-specific antibody formats, virus like particles, and possibly even cells”, says Ulrich Rant, CEO of Dynamic Biosensors.
The lever can be easily modified with desired binding sites at its top end and along its flanks and hence can serve as a scaffold for the positioning of ligand molecules with nanometer accuracy. Rant is excited the electrically powered origami lever has proven to be suited for continuous operation and believes “The big nanolever opens fascinating perspectives for advanced sensing applications, not only in the design of sensor surfaces with multiple different ligands, but also when size, shape, and conformation information is required for large targets”.
Products for High-Performance Analysis
switchSENSE® experiments are performed on reusable multi-electrode, multi-channels biochips.
Fully automated switchSENSE® instruments are 96-well plates compatible and manufactured in Germany.
Including coupling kits, starter packs, training & OQ kits, as well as buffers, solutions and other consumables.
Dr. Michael Schraeml, Head Protein and Enzyme Technologies
ROCHE DIAGNOSTICS GMBH
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