Radiogenetics – a new way to control the activity of genes and cells
Nanonews Network based on the materials of The Rockefeller University: ‘Radiogenetics’ seeks to remotely control cells and genesA group of scientists from Rockefeller University (The Rockefeller University) and Rensselaer Polytechnic Institute (Rensselaer Polytechnic Institute) is developing a system that will allow remote control of biological targets in the body of living animals – quickly, without wires, implants and chemical compounds.
In an article published in the journal Nature Medicine (Stanley et al., Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles), researchers describe the successful use of electromagnetic waves to enable insulin synthesis in mice with a diabetes model. Their system includes a natural iron oxide nanoparticle – ferritin – that activates the TRPV1 ion channel. Under the influence of radio waves or a magnetic field, this metal particle opens a channel, which ultimately activates the insulin gene. Together, these two proteins function as a nanomachine that can be used as a trigger for gene expression.
Scientists experimented with various configurations of their remote control system and found that
the best of them is based on iron oxide nanoparticles (blue) bound by a certain protein (green)
with ion channels in the cell membrane (red). Photo: The Rockefeller University.
"This method allows you to control the expression of genes in a living organism without the use of wires and can potentially be used in diseases such as hemophilia to control the synthesis of missing protein. Its two key qualitative characteristics are that the system is genetically encoded and can activate cells remotely and quickly," Jeffrey Friedman, head of the Laboratory of Molecular Genetics at Rockefeller University, comments on his development. "We are now studying whether this method can be used to control the activity of neurons as a means for non-invasive modulating the activity of nerve circuits."
Other methods have been developed for remote control of cell activity or gene expression in the body of a living animal. But their capabilities are limited. Systems that use light as an on/off signal require permanent implants or are effective only if they are close to the skin, and based on chemical compounds work slowly.
The new system, called "radiogenetics", uses a signal, in this case low-frequency radio waves or a magnetic field, to heat or move ferritin particles. They, in turn, stimulate the opening of the temperature-sensitive TRPV1 channel in the cell membrane. Through this channel, calcium ions enter the cell, activating a synthetic DNA fragment developed by scientists to turn on the expression of the underlying gene, in this case, the insulin gene.
"Ferritin, a protein–coated iron-containing molecule, is usually found throughout the body of both mice and humans, but in our experiments we modified it by placing ferritin particles in different positions to see if our results could be improved," says study participant Sarah Stanley, senior researcher at the laboratory Friedman. "We found that ferritin binding to the channel is the most effective" (fig. Nature Medicine).In an earlier study, Jeffrey Friedman and his colleagues used only radio waves as an activating signal, but now they have tested a signal associated with radio waves – a magnetic field – to stimulate insulin production, and found that it has a similar effect.
"The use of radiofrequency magnetic field is a big step forward in remote control of gene expression, as it is non–invasive and adaptive," explains Jonathan Dordick, co–director of the study, professor of chemical and biological engineering at Rensselaer Polytechnic Institute. "You don't need to embed anything – no wires, no light systems – and genes are embedded by gene therapy methods. You can make a portable device that generates a magnetic field directed to certain parts of the body and use it for the treatment of many diseases, including neurodegenerative diseases. At the moment, its possibilities seem unlimited."
The positive results obtained by the group indicate the possibility of using the new system in other areas as well. Recently, Sarah Stanley received a grant from a large-scale federal initiative aimed at creating a dynamic map of the brain. She and her colleagues plan to adapt this system to turn neurons on and off in order to study their role in the brain.
"In this study, we showed that by opening the TRPV1 channel, which allows calcium ions to enter the cell, one or another gene can be turned on. Since neurons can be depolarized by calcium and other positively charged ions, such as those controlled by the TRPV1 channel, we hope that this system will be able to effectively regulate neural activity."
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