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Scientists switch mouse’s genes off and on with radio waves

Scientists switch mouse’s genes off and on with radio waves

By Alasdair Wilkins

May 6, 2012 3:30 PM

http://io9.com/5908065/scientists-switch-mouses-genes-off-and-on-wi...

Some laboratory mice were given specially engineered insuling-producing genes. These genes were then remotely activated using radio waves. This could mean a whole new field of medical procedures in which we turn genes on and off at will.

This breakthrough is the work of geneticists at New York's Rockefeller University. It's a pretty circuitous path from the initial burst of radio waves to the activation of the gene, and there's still a lot of refinement and improvement that needs to be made before this can be used in medical treatments, but still - we're talking about the ability to modify the behavior of genes without ever going inside a patient's body. That's a potentially colossal advance.

Admittedly, while the treatment itself is totally non-invasive, the researchers did first have to inject some nanoparticles onto the mice's cells in order to affect their genes. It's a bit of a complex process, but Nature has a good explanation of just what was involved:

Friedman and his colleagues coated iron oxide nanoparticles with antibodies that bind to a modified version of the temperature-sensitive ion channel TRPV1, which sits on the surface of cells. They injected these particles into tumours grown under the skins of mice, then used the magnetic field generated by a device similar to a miniature magnetic-resonance-imaging machine to heat the nanoparticles with low-frequency radio waves. In turn, the nanoparticles heated the ion channel to its activation temperature of 42 °C. Opening the channel allowed calcium to flow into cells, triggering secondary signals that switched on an engineered calcium-sensitive gene that produces insulin. After 30 minutes of radio-wave exposure, the mice's insulin levels had increased and their blood sugar levels had dropped.

The radio waves are ideal for this sort of remote manipulation because they can pass through thick layers of tissue, and they can be easily focused by the TRPV1 channel to affect only the desired target. Lead researcher Jeffrey Friedman says that, although this particular treatment had to do with insulin production, this isn't actually meant specifically as a diabetes treatment. That's a good thing, considering this treatment is massively more inefficient than many diabetes treatments currently available. Instead, this is just meant as a general proof of concept, and insulin production happens to be one of the easier gene activities to manipulate.

Even better, the researchers have already developed a way to achieve similar, albeit weaker, results without having to inject nanoparticles at all. They have developed cells that can grow their own required nanoparticles, meaning there would be no need to give patients strange chemicals or molecules. However, as Nature explains, this would still require growing tumors inside humans to actually get these cell cultures in place, which means the treatment isn't yet ethically permissible in humans. It's definitely early days yet, but this is one seriously intriguing line of research.

Via Nature. Image by mathagraphics, via Shutterstock.

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Remote-controlled genes trigger insulin production

Nanoparticles heated by radio waves switch on genes in mice

03 May 2012

Radio waves remotely triggered the release of insulin in mice.

GEORGE STEINMETZ/SCIENCE PHOTO LIBRARY

Researchers have remotely activated genes inside living animals, a proof of concept that could one day lead to medical procedures in which patients’ genes are triggered on demand.

The work, in which a team used radio waves to switch on engineered insulin-producing genes in mice, is published today in Science1.

Jeffrey Friedman, a molecular geneticist at the Rockefeller University in New York and lead author of the study, says that in the short term, the results will lead to better tools to allow scientists to manipulate cells non-invasively. But with refinement, he thinks, clinical applications could also be possible.

Friedman and his colleagues coated iron oxide nanoparticles with antibodies that bind to a modified version of the temperature-sensitive ion channel TRPV1, which sits on the surface of cells. They injected these particles into tumours grown under the skins of mice, then used the magnetic field generated by a device similar to a miniature magnetic-resonance-imaging machine to heat the nanoparticles with low-frequency radio waves. In turn, the nanoparticles heated the ion channel to its activation temperature of 42 °C. Opening the channel allowed calcium to flow into cells, triggering secondary signals that switched on an engineered calcium-sensitive gene that produces insulin.

After 30 minutes of radio-wave exposure, the mice's insulin levels had increased and their blood sugar levels had dropped.

Radio stars

“The great thing about this system is that radio-wave heating can penetrate deep tissue, and TRPV1 can focus that stimulus very locally to just where you have the nanoparticles,” says David Julius, a physiologist who studies TRPV1 at the University of California, San Francisco. 

Friedman says that his team did not develop the method as a way of managing diabetes; insulin and blood sugar levels simply provide convenient physiological readouts for checking that the remote control is working. “There are many good treatments for diabetes that are much simpler,” he says. However, the system could potentially be engineered to produce proteins to treat other conditions.

In control experiments, the researchers showed that the radio waves heated only cells that contained nanoparticles, and the heat neither killed the specialized cells nor spread to neighbouring, unmodified ones. “Magnetic fields are a good way to develop enough energy without doing harm,” says Arnd Pralle, a biophysicist at the State University of New York at Buffalo, who has worked on stimulating neurons using nanoparticles heated by radio waves2. However, he says, more research is needed to characterize fully how the nanoparticles absorb, retain and distribute heat.

Genetic therapy

The researchers also experimented with cultured cells genetically engineered to make their own nanoparticles, and found that they could stimulate a weaker insulin secretion in these cells, too. “What I found most novel about this is there’s no need for any chemicals or small molecules to be administered,” says Ed Boyden, a neurobiologist at the Massachusetts Institute of Technology in Cambridge, who helped to pioneer a method of using fibre optics to control neural activity with light3.

Friedman's current method is not practical for use in the clinic because it is not ethical to grow tumours in humans, so the researchers are planning to test alternative delivery systems for the nanoparticles.

“I think people intuit that someday nanotechnology will have an impact on human medicine,” says Friedman. “We’ve extended the repertoire of what the particles can do in living animals.”

Nature
doi:10.1038/nature.2012.10585

References

  1. Stanley, S. A., et al. Science 336, 604608 (2012).

  2. Huang, H., Delikanli, S., Zeng, H., Ferkey, D. M. & Pralle, A. Nature Nanotechnol. 5, 602606 (2010).

  3. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Nature Neurosci. 8, 12631268 (2005)

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