Play of colors on demand
Drug monitoring made easily available using tunable luciferases
In treating various diseases with medication, it is increasingly important to be able to monitor the level of certain drugs in the patient’s body, as continuously as possible and outside of the laboratory, ideally by on-going measurement e.g. in the blood. Scientist from the Max Planck Institute for medical Research have recently developed a sensor based on tunable luciferases to enable those measurements at any patients home while also creating a powerful tool for bioimaging.
Such devices often operate by measurement of light signals from e.g. the blood, and here luciferases play an important role. They are protein molecules that show bioluminescence, as in the natural luminescence of e.g. glow-worms. Nanoluc is an example of a synthetic, particularly intense luciferase who emits blue light (wavelength around 460 nanometers). A practical problem, however, is that blue light is not easily measured in e.g. blood, because it is strongly absorbed by the surrounding material.
The usefulness of luciferase as a signal molecule would increase significantly without this limitation, and here the group of Kai Johnsson at the MPI has made a significant development of a system (LUCiferase-based Indicators of Drugs, LUCIDs) they invented before. Each luciferase can be tagged with a second small, colorful molecule (fluorophore), which likewise produces light, such that between the two light-producing centers an interaction occurs: this interaction shifts the wavelength of the emitted light into another region, depending on the small molecule that is added. `This includes a shift to the red region, which can be measured more easily by simple sensors`, says Julien Hiblot, senior scientist at the department of Kai Johnsson and co-author of the paper.
Drug sensors in blood
Such a system can then be easily adapted to the measurement of drug levels by the addition of a binding site for a specific compound (or very similar molecules). A built-in copy of the drug occupies this site but can be displaced by competition from free drug molecules in the vicinity. The concentration of the drug in the vicinity then determines the probability that the bound drug molecule is displaced and hence the color of the resulting light.
The expertise of Johnsson’s group in designing fluorescent molecules has allowed them to produce a variety of different Nanoluc-based systems for applications with a variety of practical clinical requirements. The system can also be used to monitor different substances simultaneously. `That makes it an important tool for biosensing but also opens up new opportunities in bioimaging`, explains Kai Johnsson.