Nanoparticle-cell interface enables electromagnetic wireless programming of mammalian transgene expression

Recent technological advances are fueling the development of cutting-edge technologies that can monitor and control physiological processes with high precision. These include devices that could control the expression of genes within living organisms, without requiring invasive surgeries or procedures.

Researchers at ETH Zurich recently introduced a new method that enables the electromagnetic programming of the wireless expression regulation (EMPOWER) of transgenes in mammals, via the interfacing of nanoparticles and cells.

Their proposed approach, outlined in a paper published in Nature Nanotechnology, could help to treat chronic conditions, including diabetes, while also opening new possibilities for research in synthetic biology and regenerative medicine.

“Our recent study is all about tackling the ongoing challenge in biomedicine of precisely and non-invasively controlling therapeutic gene expression within living organisms,” Martin Fussenegger, senior author of the paper, told Phys.org.

“I understand that conventional methods can be a bit tricky. Either they require invasive procedures, or they might not be as precise or robust as we’d like. This inspired us to use magnetic fields for wireless control, taking advantage of their ability to penetrate biological tissues safely and effectively without direct contact or invasive devices.”

The main objective of the recent study by Fussenegger and their colleagues was to devise a safe and robust approach to reliably control the amount of a therapeutic protein produced by mammals from a distance. The method they introduced in their paper relies on nanoparticles made of multiferroic materials, which were coated with a biocompatible polymer called chitosan.

“When these nanoparticles are stimulated by a low-frequency magnetic field, they generate biosafe levels of reactive oxygen species (ROS) within the cell cytoplasm,” explained Fussenegger.

“We engineered mammalian cells to include a genetic circuit that’s sensitive to these ROS signals, using the cellular KEAP1/NRF2 pathway. When ROS are detected, it’s like a signal to NRF2 proteins to get busy, and they work together to bring selected therapeutic proteins, like insulin, to life.”

A key advantage of the nanoparticle-cell interface introduced by Fussenegger and his colleagues is that it enables precise control over when and where one wants a gene to be expressed. In addition, the method is gentle and non-invasive, as it does not require demanding procedures or high-energy stimulation.

Compared to other previously proposed nanoparticle-based methods for the wireless control of gene expression, the team’s approach is highly bio-compatible and requires lower nanoparticle dosages, while also minimizing off-target effects. To demonstrate its potential, the researchers tested it on a mouse model of diabetes.

“In this experiment, we exposed mice to a weak electromagnetic field (1 kHz, 21 mT) for just three minutes each day,” said Fussenegger.

“This controlled their insulin secretion really well and kept their blood glucose levels normal during the whole study. We’re so excited to share the most significant achievement of our study: we’ve successfully connected wireless electromagnetic controls to natural transgene expression in mammalian cells via intracellular nanoparticles as interfacial magnetic receivers.”

The nanoparticles utilized by the researchers were introduced in the cytoplasm, the jelly-like substance that surrounds the nucleus in cells. This allowed the nanoparticles to communicate with the cells, leveraging chemical reactive oxygen species (ROS), a class of reactive oxygen-containing molecules naturally produced in cells.

“This was true even when the nanoparticles were interacting directly with the proteins,” said Fussenegger. “Our construction is great because it gets the cells working together, and it does this without disrupting the integrity of engineered cells. This helps us get the results we need, but without any of the problems.”

The nanoparticle-cell interface devised by this team of researchers could have highly valuable medical applications. Notably, the approach utilizes a very weak electromagnetic field (below 1 kHz) and low power (21 mT), while stimulating cells for a very short time (three minutes).

“This is much weaker than the levels used in clinical MRI scans,” said Fussenegger. “Our approach could thus be highly valuable for managing chronic diseases, as it would let us adjust therapy remotely and dynamically. This would eliminate the need for repeated injections, invasive implants or systemic drug administration.”

In the future, the team’s approach for remotely controlling transgene expression could be tested and implemented in clinical settings. The researchers are now exploring the potential application of their method in the fields of oncology, neurology and regenerative medicine, while also working on improving their nanoparticle-based system.

“In our next studies, we’re going to focus on making our system even more sensitive, biocompatible and efficient,” added Fussenegger.

“We’re also planning to make some improvements to the electromagnetic stimulation equipment. We want to make it more compact so it’s easier to use in a clinical setting.

“We’re looking forward to doing even more in the future. We’re going to use this platform for other chronic diseases. We’re also going to explore alternative genetic circuits. And we’re going to get the technology ready for preclinical and clinical evaluation.”

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