NanoLoom: a high-throughput platform for in vitro screening of modulators of mitochondrial replisome activity

Mitochondrial diseases affect thousands of people worldwide, often leading to severe health problems with no effective treatment options. These diseases can be caused by mutations in POLG, an essential protein that helps copy mitochondrial DNA. Up to 2% of the population carries a POLG mutation, and in 10% of mitochondrial disease cases, these mutations cause debilitating symptoms, including muscle weakness, neurological disorders, and organ failure. Currently, treatment is limited to supportive care, and there is an urgent need for new therapies to help patients.

To address this challenge, 1NA and LPCA have joined forces to develop an innovative screening method for drugs that could restore POLG function. Traditional drug screening methods are slow and limited in scope. In this project, we use a high-tech device that aligns thousands of DNA molecules in a single experiment, making it possible to rapidly analyse drug effects on POLG at the molecular level. This approach increases screening efficiency, making it easier to find promising drug candidates.

The project will test known drug molecules that have shown potential to stimulate POLG activity. By identifying drugs that enhance POLG function, this research could lay the groundwork for future treatments for mitochondrial diseases. The developed high-throughput DNA analysis method may also be applied to study other disease-related proteins, making it a valuable tool for broader drug discovery efforts.

By the end of the project, the results will help scientists and pharmaceutical companies identify and validate potential drugs faster and more effectively. This collaboration between 1NA and LPCA demonstrates how advanced single-molecule techniques can revolutionize drug discovery, potentially offering new hope for patients suffering from mitochondrial diseases.