New Study Highlights Depixus' Platform in Advancing RNA-Targeted Drug Development

A recent study, published in Nature Communications, has underscored the potential of Depixus’ innovative single molecule technology in shedding light on RNA-ligand binding mechanisms, which could be instrumental in advancing new therapies. Utilizing magnetic force spectroscopy (MFS), Depixus’ large-scale interactomics platform stands as the pioneering analytical technology capable of examining dynamic biomolecular interactions in real time and simultaneously across thousands of individual molecules.

The research was spearheaded by Dr. John “Jay” Schneekloth, Jr., a prominent figure in RNA-targeted drug discovery at the National Cancer Institute, a segment of the US National Institutes of Health. The study utilized Depixus' scalable MFS platform to delve into the interactions between the Bacillus subtilis (Bsu) PreQ1 bacterial riboswitch and its natural ligand, PreQ1, as well as a synthetic small molecule known as Compound 4.

Riboswitches are structured RNA sequences commonly located in the 5′ untranslated regions of bacterial mRNAs, playing a crucial role in regulating metabolic pathways. When ligands such as metabolites bind to riboswitches, they trigger a conformational shift in the RNA's secondary structure, thereby influencing gene expression. These characteristics make riboswitches a promising target for novel antibacterial drugs.

A significant part of the study involved using Depixus' MFS platform to meticulously measure the effects of PreQ1 and Compound 4 binding on immobilized target riboswitch RNA aptamers. The findings indicated that both ligands contributed to stabilizing the RNA structure, with the impact of varying compound concentrations also being assessed.

Crucially, analyzing data streams from individual interactions unveiled that the two ligands operated through distinctly different mechanisms - a critical insight that could be overlooked by other analytical methods that only provide averaged or surrogate measurements.

Jimmy Ouellet, Chief Scientist at Depixus, emphasized the importance of this capability, stating, “This study showcases how our capacity to independently analyze individual biomolecular interactions allows us to observe RNA-ligand interactions in real time, offering valuable insights into distinct mechanisms of action. With our large-scale MFS platform, we now possess a technology that can observe biological processes as they occur, investigating the mechanistic effects of compounds on their targets at the individual molecule level and generating detailed information about binding kinetics and more.”

Depixus’ distinctive platform delivers crucial data about a vast array of individual dynamic molecular interactions, including those between RNA, DNA, proteins, and small molecules. This technology deciphers disease mechanisms and accelerates the development of more effective therapies.