Humanized Bacterial Luciferase

Molecular biologists insert bioluminescent genes into cells to report back on any number of measures, such as the toxicity or efficacy of a drug. Firefly luciferases are popular reporter proteins, but they have one glaring deficiency: exogenous reagents must be added to target cells to turn on their glow, thus killing the cells and halting the experiment. This means that toxicity, for instance, can’t be measured continuously over the course of a drug’s dose, but only at discrete time points.
Bacterial luciferase, on the other hand, “is its own little machine,” says Steve Ripp, the COO of 490 BioTech, a company that has developed a bioluminescent reporter system that requires no additional substrate to turn on the light. “No more killing your cells to get the substrate into your cell,” he says.
490 BioTech has introduced bacterial luciferase into various eukaryotic cell lines, including a number of human lines, and the reporter can be custom-made for specific experiments. “You tell us what you need, what cell line, what you want that cell line to do, and we will design it and sell it to you,” says Ripp. Costs range from $8,000 to $22,000.
Although the signal is not as strong as those of other luciferases, the product works especially well for 3-D drug screens, for which assays have proven a challenge to develop, says Hal Crosswell, the chief medical officer of Kiyatec, a company that has worked with 490 Biotech on testing applications of the reporter cells. “The fact that you can monitor these in real time, continuously, without ending the experiment, is huge.”

MARDIS: It transitions a critical tool from the bacterial to the mammalian world—magic!

LUSTIG: This is a significant new addition to the bioluminescent assay tool kit in widespread use in pharma and academia. Eukaryotic cell lines that self-bioluminesce will enable new research approaches, including continuous imaging in cell and animal models of disease.
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