Remotely and Noninvasively Controlling Genes and Cells in Living Animals

Remote control car key.
Researchers are developing a system to remotely control genes or cells in living animals with radio wave technology similar to that used to operate remote control car keys. Credit: Stock image.

One of the items on biomedical researchers’ “to-do” list is devising noninvasive ways to control the activity of specific genes or cells in order to study what those genes or cells do and, ultimately, to treat a range of human diseases and disorders.

A team of scientists recently reported progress on a new, noninvasive system that could remotely and rapidly control biological targets in living animals. The system can be activated remotely using either low-frequency radio waves or a magnetic field. Similar radio wave technology operates automatic garage-door openers and remote control car keys and is used in medicine to control electronic pacemakers noninvasively. Magnetic fields are used to activate sensors in burglar alarm systems and to turn your laptop to hibernate mode when the cover is closed.

One of the two components of the new system is a natural iron storage particle called ferritin. This particle is tethered to a temperature-sensitive channel protein that controls the flow of calcium into a cell. Together, the two molecules work as a nano-machine that can be used to trigger gene activity, or expression, in cells. When the ferritin particle is exposed to radio waves or a magnetic field, it opens the channel, activating a gene engineered to respond to calcium.

The researchers found that radio waves and magnets may have different ways of causing the calcium channel to open. Low-frequency radio waves cause mild heating of the ferritin’s iron core, tripping a switch that opens the channel, while the tug of a magnetic field most likely causes the ferritin particles to move slightly and nudge the channel open. Calcium then flows into the cell and turns on the calcium-responsive gene.

As proof of principle, the team, led by Jeffrey Friedman Exit icon at Rockefeller University and Jonathan Dordick Exit icon at Rensselaer Polytechnic Institute, showed that they could use their system to turn on insulin production and thereby lower blood sugar in diabetic mice. The researchers used genetic techniques to introduce the ferritin-tethered channels into mice along with a calcium-responsive version of the insulin gene.

In a news release, Friedman says that the system could potentially be used to control the production of a missing protein in conditions like hemophilia or to control neural activity in the brain. Indeed, another member of the research team, Sarah Stanley of Rockefeller University, is leading a follow-up study to adapt the system to switch neurons on and off so she can study their roles within the brain.

While other techniques exist for remotely controlling gene expression or cell activity in living animals, those methods have limitations. Systems that use light as an on/off signal require permanent implants or are only effective close to the skin, and those that rely on drugs can be slow to switch on and off.

In a commentary on the new study, Ingo Leibiger and Per-Olof Berggren of Sweden’s Karolinska Institute write: “A genetically encoded switch to control biological systems in the living organism by either low-frequency radio waves or by a magnetic field is an exciting noninvasive approach with many potential applications.”

This research was funded in part by NIH under grants R01GM095654 and T32GM067545.

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