Shedding light on a molecular marker of physiological aging
Scientists develop a light-emitting biosensor for the point-of-care quantification of a central biochemical cofactor
At present, NAD+ levels in cells are routinely measured by mass spectrometry or enzymatic assays. However, both methods are labor-intensive and require expensive equipment, making them unsuitable for point-of-care applications at patients’ homes or on the go. To address these limitations, Dr. Qiuliyang Yu from the Department of Chemical Biology at the Max Planck Institute for Medical Research designed a semisynthetic, light-emitting sensor protein. The color of emitted light changes from blue to red upon binding to NAD+. This NAD+-dependent color change enables the use of the biosensor in paper-based assays in which NAD+ is quantified, by simply measuring the color of the emitted light using a regular digital camera. It requires only a very small amount of sample, such as a drop of blood, and a few seconds to get the results, which also makes it a promising tool for point-of-care applications.
According to Dr. Yu, “the biggest challenge was to optimize the sensor to a point where it was accurate and consistent enough for measuring clinical samples. To improve the sensitivity, we screened a large number of mutants to identify the protein variant that fitted our need.”
Testing the new tool, scientists at the MPI for Medical Research and EPFL quantified NAD+ levels in cell culture, tissue and blood samples, yielding results that agreed with standard testing methods. “The simplicity of the approach should greatly facilitate basic research on this vital cofactor,” says Qiuliyang Yu. “And I am particularly excited about the idea of developing a point-of-care system for patient self-testing. This would enable us to study the role of NAD+ levels in physiological aging and neurodegenerative diseases.”
The MPI for Medical Research has now started a collaboration with scientists at the Fraunhofer Institute of Cell Therapy and Immunology to develop a more automated version of the paper-based assay. “This is a great opportunity for us to bring the biosensor into the clinic and to patients,” says Dr. Corentin Gondrand, a co-author of the paper and project coordinator of the collaboration with the scientists at the Fraunhofer Institute. A broad availability of the biosensor will advance research on the role of NAD+ in health and disease.