Single-molecule techniques provide unparalleled insight into molecular interactions between proteins and DNA. ThThe NanoLoom platform will use advanced DNA curtain technology and DNA-PAINT labeling to observe DNA-protein interactions across thousands of DNA molecules simultaneously. This will create an unparalleled in vitro environment for evaluating the efficacy and mechanisms of new and existing drugs. As part of the Biotech Booster program, we will refine and validate the NanoLoom workflow with Dr. Kristina Ganzinger from AMOLF. We will conduct proof-of-concept studies using RNA polymerase from Mycobacterium tuberculosis to showcase the platform’s potential in drug repurposing. Additionally, we will optimize data analysis, validate the market, and prepare for broader applications in academic research and pharmaceutical development.ese techniques hold tremendous promise for drug discovery by enabling high-resolution studies at the molecular level.

In this project, we will use our device to study drugs that enhance motor protein activity, focusing on mutated mitochondrial human polymerase POLG. POLG mutations are the leading cause of inherited mitochondrial diseases, responsible for 10% of cases. Up to 2% of the population carries these mutations. Despite their prevalence, treatments remain scarce and are mostly limited to symptomatic care. We will test recently identified molecules that stimulate POLG activity in vitro. This collaboration between .1NA and Dr. Geraldine Farge (LPCA, France) will combine expertise in mitochondrial DNA replication and single-molecule techniques. Together, we will adapt and validate this innovative approach.