Ultrasonic combined with gene editing! Can be used for potential non-invasive clinical applications such as pacemaker replacement

A team of researchers from the United States has developed a new "acoustic genetics" technique that uses sound to activate and control mammalian cells that has the potential to pave the way for innovative, non-invasive deep brain stimulators, pacemakers and insulin pumps. What exactly is sonogenetics and what are the potential clinical advantages? What is the next goal of the research team?

Ultrasound stimulation

This new technique combines ultrasound and gene therapy to deliver genes to specific cells, manipulating them with sound to achieve therapeutic effects. The results of the study, published in the journal Nature Communications, show how the team used this method to activate human cells in a dish and how neurons in the mouse brain and spinal cord could be controlled.

Screenshot of the paper

"Acoustic genetics uses ultrasound to control specific cells." Dr. Sreekanth Chalasani from the Salk Institute of Biology explains. "Ultrasound is sound, and its nature is mechanical, so it causes a small amount of mechanical deflection in the area of focus, and we found an ion channel protein that can sense this mechanical deflection." Thus, we can express this ion channel on the cells we want to control. ”

To test the technique, the researchers introduced a gene for an ion channel protein (TRPA1) into target cells. After expressing this ion channel, these target cells begin to become sensitive to ultrasound. In addition, in the study conducted on mice, the team was able to control target cells through ultrasonic stimulation after attaching the sensor to the skin of the mouse. "This ion channel doesn't usually appear on cells, so by artificially adding this protein to cells, we introduce a new cellular function." Chalasani added.

Potential clinical applications

According to Chalasani, acoustic genetics has some key advantages over other more invasive treatments. First, in simple terms, this new technology shows how motor neurons in the cerebral cortex move limbs, which is also a predictable result. Chalasani also pointed to a range of potential non-invasive clinical applications that the technology could lead to, including replacing deep brain stimulators, pacemakers, and insulin pumps.

"Pacemakers may be the first clinical application of the technology, given that the gene delivery system we currently have in place can deliver genes to human cardiomyocytes." However, there is no way to pass genes into the human brain. Chalasani said.

Today's treatments involve surgery and implantation of devices in the body, which increases the risk of infection and inflammation. "Since the sensor works outside the body, our method does not require implantation. All we do is deliver the protein to the target cell. Chalasani explained.

Chalasani said he and his team are already trying to take these findings one step further and hope to find proteins that are more sensitive to ultrasound, not only respond to specific frequencies of ultrasound, but also inhibit neurons, rather than just stimulating neurons like the proteins found so far.

Chalasani told Physical World: "We want to continue to innovate ultrasound transmission devices in order to transmit the appropriate ultrasound stimuli to targets in the brain or body. Although we are currently only studying in mice, we hope to experiment with large animals such as pigs or primates before applying this technique to humans. ”

bibliography

[1] Controlling cells with sound: Scientists pioneer sonogenetics. (2022, March 4). Physics World. https://physicsworld.com/?p=99748

[2] Duque, M., Lee-Kubli, C. A., Tufail, Y., Magaram, U., Patel, J., Chakraborty, A., Mendoza Lopez, J., Edsinger, E., Vasan, A., Shiao, R., Weiss, C., Friend, J., & Chalasani, S. H. (2022). Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels. Nature Communications, 13(1), 600. https://doi.org/10.1038/s41467-022-28205-y

Originally written by Abigail Williams, freelance journalist

Compiler: Zhang Mingyu

Edit: Crispy fish

Typography: Yin Ningliu

Source: Reference [1] (Mouse brain cell neurons are ultrasonically activated after expression of the protein TRPA1)

Research team

Corresponding author Sreekanth H. Chalasani: Assistant Professor, Laboratory of Molecular Neurobiology, Salk Institute of Biology, USA

First author Marc Duque: PhD student in neuroscience at Harvard University

Second author Corinne A. Lee-Kubli: Scientist at DTx Pharma, an American biotech company

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