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Researchers at Salk Institute for Biological Studies, California, have engineered mammalian cells that can be controlled with ultrasound. The method used by the team can support non-invasive treatment methods where no medical devices are inserted into the body to treat conditions, nor is there a need to undergo surgeries. This new technique can be used to develop non-invasive forms of pacemakers and insulin pumps for future use.
“Going wireless is the future for just about everything,” said Sreekanth Chalasani, associate professor at Salk Institute. “We already know that ultrasound is safe, and it can go through bone, muscle, and other tissues, making it the ultimate tool for manipulating cells deep in the body.”
Ten years ago, Chalasani got an idea of using ultrasound to activate a specific group of cells. Later, he coined the term “Sonogenetics” to describe this process. In medicine, Sonogentics is the use of ultrasound to manipulate neurons and other cells non-invasively.
Earlier, his team discovered a cell protein called TRP-4 in roundworms. This protein was sensitive to ultrasound. Researchers extracted TRP-4 and transferred it to roundworms’ neurons that they usually didn’t have. Then, they tried to activate these neurons with ultrasound and the neurons responded.
Similarly, they added this protein to mammalian cells but got negative results. The protein was not able to make the cells respond. Thereupon, Chalsani and his team tried to discover mammalian cells that were sensitive to ultrasound. They kept the frequency at 7MHz for the experiment as it is a safe and optimal frequency.
Researchers added different proteins to human cell lines (cell cultures used for experiment). They exposed these cells to ultrasound and observed their behaviour. Finally, they were able to engineer a cell line that was sensitive to the 7MHz frequency of ultrasound. They found that a protein called TRPA1 was responsible for activating cells and responding. Also, it was found for activating various cells in the human body including heart and brain cells.
Further, they used a gene therapy approach to test whether the protein could activate other cells in response to ultrasound. They added the protein TRPA1 to a targeted group of neurons in the living mice. When the mice were exposed to ultrasound, only neurons with TRPA1 genes were activated.
Presently, treatment options for neurological disorders such as Parkinson’s disease and epilepsy include deep brain stimulation techniques in which electrodes are inserted surgically in the brain to stimulate neurons. Chalasani said that sonogentics could replace these conventional treatment options someday. It could be used to activate heart cells as a pacemaker that would not need to be surgically implanted.
“Gene delivery techniques already exist for getting a new gene- such as TRPA1- into the human heart,” said Chalasani. “If we can then use an external ultrasound device to activate those cells that could really revolutionize pacemakers.”
Currently, the team is working to know how TRPA1 senses ultrasound. “In order to make this finding more useful for future research and clinical applications, we hope to determine exactly what parts of TRPA1 contribute to its ultrasound sensitivity and tweak them to enhance this sensitivity,” said Corinne Lee-Kubli, a co-first author of the paper and former postdoctoral fellow at Salk.
They are also planning to look for proteins that can inhibit the activity of cells in the presence of ultrasound.
The complete research has been published in the journal Nature Communications.
Contributed by: Simran Dolwani
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