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Genetic Clock
Engineered mammalian cells keep time

Source: “A tunable synthetic mammalian oscillator”
Martin Fussenegger et al.
Nature
457: 309-312

Results: Scientists at the Swiss Federal Institute of ­Technology Zürich genetically engineered a molecular oscillator that turned the production of a fluorescent protein in a hamster cell on and off every two to three hours for more than 20 hours. Changing the amount of DNA added to the cells varied the frequency of the oscillations.

Why it matters: Genetic oscillators could have numerous applications in genetic engineering and drug delivery. The clock might be adapted to deliver a protein drug; the frequency and amplitude of the oscillations would determine the dose of the drug and how often it was delivered. The findings may also help scientists understand the molecular clocks mediating numerous biological functions, such as circadian rhythm.

Methods: Researchers modified the hamster cells with DNA containing the code for a specific gene and the complement of that code. Turning on that gene creates an RNA transcript for a transcription factor, a protein that in turn activates production of a fluorescent protein and a second transcription factor. An excess of the second transcription factor activates the complementary code, which produces the mirror image of the original RNA transcript. This mirror transcript binds to the original RNA transcript, stopping the production of the fluorescent protein and the second transcription factor. Without the second transcription factor, the mirror transcript is no longer produced, and the concentration of the regular gene transcript begins to build again.

Next steps: The researchers are now trying to get the oscillator to function synchronously in an entire population of cells, which will be necessary if it is to be used for drug delivery.

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Credit: Alison Skelley

Tagged: Biomedicine

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