Hong Chen and her team plan to integrate ultrasound with genetics to precisely modify neurons in the brain with their Sonogenetics 2.0 technology.
Researchers at Washington University in St. Louis have innovated a noninvasive technology that merges a holographic acoustic device with genetic engineering. This enables them to target specific neurons within the brain accurately.
This breakthrough holds promise for the precise modulation of targeted cell types across various diseased brain regions.
Diseases of the human brain, such as Parkinson’s, affect multiple regions, necessitating technology capable of precisely and flexibly addressing all impacted areas simultaneously.
“By enabling precise and flexible cell-type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders,” Hong Chen, an associate professor of biomedical engineering at the McKelvey School of Engineering and of neurosurgery at the School of Medicine, said.
A noninvasive wearable ultrasound device
Chen and her team developed a technique called AhSonogenetics, or Airy-beam holographic sonogenetics. This method employs a noninvasive wearable ultrasound device to modify genetically selected neurons in mouse brains.
AhSonogenetics integrates several of Chen’s group’s recent breakthroughs into a single technology. In 2021, Chen and her team introduced Sonogenetics, a method utilizing focused ultrasound to deliver a viral construct containing ultrasound-sensitive ion channels to genetically selected neurons in the brain.
This technique employs low-intensity focused ultrasound to produce a brief burst of warmth, opening the ion channels and activating the neurons. Chen’s team was the first to demonstrate that sonogenetics could influence the behavior of freely moving mice.
In 2022, Chen and her lab members designed and 3D-printed a flexible and versatile device called an Airy beam-enabled binary acoustic metasurface, which allowed them to manipulate ultrasound beams.
Additionally, she is working on Sonogenetics 2.0, a technique that combines the benefits of ultrasound and genetic engineering to noninvasively and precisely modulate specific neurons in the brains of humans and animals.
Sonogenetics: The tech behind the device
Sonogenetics provides researchers with a precise method to control brain activity, while airy-beam technology enables the bending or steering of sound waves to create arbitrary beam patterns within the brain with high spatial resolution.
According to Yaoheng Yang, a postdoctoral research associate who earned his doctorate in biomedical engineering from McKelvey Engineering in 2022, this technology offers three distinct advantages to researchers.
“Airy beam is the technology that can give us precise targeting of a smaller region than conventional technology, the flexibility to steer to the targeted brain regions, and to target multiple brain regions simultaneously,” Yang said.
Chen and her team, including first authors Zhongtao Hu, a former postdoctoral research associate, and Yaoheng (Mack) Yang, individually designed each Airy-beam metasurface to serve as the basis for wearable ultrasound devices tailored for various applications and precise brain locations.
The team tested the technique on a mouse model of Parkinson’s disease. Using AhSonogenetics, they successfully stimulated two brain regions simultaneously in a single mouse, removing the need for multiple implants or interventions. This stimulation alleviated Parkinson’s-related motor deficits in the mouse model, such as slow movements, difficulty walking, and freezing behaviors.
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The findings of the proof-of-concept study were published in the Proceedings of the National Academy of Sciences.
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