Abstract: Technologies currently used to study the dynamics of biomolecular interactions typically generate results at a bulk level, with data being averaged from across all molecules in a sample. As a result, biological variability often cannot be revealed and important signals coming from molecular sub-populations are lost.
Single-molecule approaches can provide new views into what is happening at a true molecular level including, for example, visualising the real-time conformational dynamics of a molecule. When performed at scale the data sets generated will have the potential to open up new biological insights and novel routes to developing more effective therapies.
MAGNA™ is a ground-breaking technology, being developed by the company Depixus, which uses magnetic force spectroscopy to measure and characterise the dynamics of interactions in real-time across thousands of individual molecules.
We will be introducing the general principles behind how MAGNA™ works and will describe several different ways in which biomolecular interactions can be analysed with the technology. Using recent data, we will show how MAGNA™ can detect the precise locations and kinetics of oligonucleotide binding to nucleic acid targets; how three-dimensional structures on nucleic acids can be stabilized or destabilized by proteins and/or small molecules; and how protein-protein interactions can be analysed in real-time. We will highlight the relevance of these results to the development of improved ASOs, RNA small-molecule therapeutics, and molecular glues and/or degraders, respectively.
The data presented will illustrate the versatility of the MAGNA™ approach and how, by measuring the changes in the biophysical properties of individual molecules, it is possible to generate content-rich structural and kinetic information for many biological interactions across multiple molecule types.