rexresearch
Sonogenetics

https://sonogenetics.salk.edu/
Sonogenetics -- Controlling brain cells with sound wave

Sonogenetics is a rapidly evolving field that leverages the power of low-intensity ultrasound to achieve precise, non-invasive control over cellular activity. By engineering mechanosensitive proteins, researchers can now render specific cells sensitive to acoustic pressure, bypassing the need for invasive implants or tethered light sources. This technology represents a fundamental shift in our ability to probe and treat complex biological systems across both neuronal and non-neuronal circuits. From uncovering the basic principles of brain function to the development of targeted human therapeutics, sonogenetics is redefining the boundaries of neuromodulation.

https://www.youtube.com/watch?v=tNnRd0JfT4o
Progress for Sonogenetics a non-invasive way to treat brain disorders

https://ieeexplore.ieee.org/document/11249725
Introduction to Sonogenetics for Ultrasound Scientists
Walsh, Yoon, Anderson, et al.

A comprehensive review explaining the principles of sonogenetics...

https://www.nature.com/articles/ncomms9264
Nature Communications, 2015
Sonogenetics is a non-invasive approach to activating neurons in C. elegans
Ibsen et al.,

TRP-4 can sensitize specific neurons to low-pressure ultrasound to enable behavioral control in freely moving animals.

https://www.nature.com/articles/s41467-022-28205-y
Nature Communications, 2022
Sonogenetic control of mammalian cells using exogenous TRPA1 channels
Duque et al.

Human TRPA1 (hsTRPA1) can be used as a sonogenetic actuator to achieve ultrasound-dependent calcium influx and neural activation in mammalian systems, both in vitro and in vivo.

https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202101950
Advanced Science, 2022
Ultrasound Mediated Cellular Deflection Results in Cellular Depolarization
Vasan et al.
[ PDF ]

Uses high-speed digital holographic microscopy to quantify ultrasound-induced membrane deflection, providing evidence for the mechanical forces required to gate sonogenetic channels.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267698
Two parallel pathways are required for ultrasound-evoked behavioral changes
Magaram et al.

Investigates the interaction between sonogenetic tools and natural mechanosensory pathways, showing how multiple channels contribute to ultrasound-evoked behavior in C. elegans.

https://www.nature.com/articles/ncomms9264
Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans
Stuart Ibsen, et al

Abstract -- A major challenge in neuroscience is to reliably activate individual neurons, particularly those in deeper brain regions. Current optogenetic approaches require invasive surgical procedures to deliver light of specific wavelengths to target cells to activate or silence them. Here, we demonstrate the use of low-pressure ultrasound as a non-invasive trigger to activate specific ultrasonically sensitized neurons in the nematode, Caenorhabditis elegans. We first show that wild-type animals are insensitive to low-pressure ultrasound and require gas-filled microbubbles to transduce the ultrasound wave. We find that neuron-specific misexpression of TRP-4, the pore-forming subunit of a mechanotransduction channel, sensitizes neurons to ultrasound stimulus, resulting in behavioural outputs. Furthermore, we use this approach to manipulate the function of sensory neurons and interneurons and identify a role for PVD sensory neurons in modifying locomotory behaviours. We suggest that this method can be broadly applied to manipulate cellular functions in vivo

https://www.sciencedirect.com/science/article/pii/S1935861X22002066
Sonogenetics: Recent advances and future directions
Tianyi Liu, et al
[ PDF ]

Abstract-- Sonogenetics refers to the use of genetically encoded, ultrasound-responsive mediators for noninvasive and selective control of neural activity. It is a promising tool for studying neural circuits. However, due to its infancy, basic studies and developments are still underway, including gauging key in vivo performance metrics such as spatiotemporal resolution, selectivity, specificity, and safety. In this paper, we summarize recent findings on sonogenetics to highlight technical hurdles that have been cleared, challenges that remain, and future directions for optimization.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11373633/
The principles and promising future of sonogenetics for precision medicine
Pengying Wu et al
[ PDF ]

Abstract -- Sonogenetics is an emerging medical technology that uses acoustic waves to control cells through sonosensitive mediators (SSMs) that are genetically encoded, thus remotely and non-invasively modulating specific molecular events and/or biomolecular functions. Sonogenetics has opened new opportunities for targeted spatiotemporal manipulation in the field of gene and cell-based therapies due to its inherent advantages, such as its noninvasive nature, high level of safety, and deep tissue penetration. Sonogenetics holds impressive potential in a wide range of applications, from tumor immunotherapy and mitigation of Parkinsonian symptoms to the modulation of neural reward pathway, and restoration of vision. This review provides a detailed overview of the mechanisms and classifications of established sonogenetics systems and summarizes their applications in disease treatment and management. The review concludes by highlighting the challenges that hinder the further progress of sonogenetics, paving the way for future advances.

Patents

US2019217128 --  SYSTEM AND METHOD FOR SONOGENETIC THERAPY
One embodiment is directed to an implantable probe system for delivering acoustical energy to a targeted tissue portion of a patient, comprising: a plurality of substrate portions, each substrate portion comprising at least one acoustical emitter; a probe body portion having proximal and distal ends and being movably coupled to the plurality of substrates and configured to at least partially encapsulate the plurality of substrates; and a distal end portion coupled to the distal end of the probe body portion, the distal end portion comprising at least one guiding feature configured to redirect a path of at least one of the substrate portions as such substrate portion is extended through and past the distal end portion by moving the plurality of substrates relative to the probe body portion.

US2019321473 --  MINIMALLY-INVASIVE, HIGH RESOLUTION NEUROMODULATION OF DEEP BRAIN AND CORTICAL STRUCTURES USING CIRCUIT-SPECIFIC PROMOTERS AND FOCUSED ULTRASOUND ARRAY
One embodiment is directed to a method for treating the nervous system of a patient, comprising: determining a desired nervous system functional modulation to be facilitated by sonogenetic intervention; selecting targeted neuroanatomy for achieving the desired functional outcome with sonogenetic intervention; and delivering an effective amount of polynucleotide comprising a sound-responsive opsin protein which is expressed in neurons of the targeted neuroanatomy, wherein delivering comprises systemically injecting the effective amount of polynucleotide and facilitating diffusive access to the targeted neuroanatomy using focused ultrasound energy

WO2024197304 -- ADVANCED FUNCTION STENT SYSTEM FOR CHRONIC ON-DEMAND DRUG DELIVERY, SONOGENETIC CONTROL OF CELLS, AND ACOUSTIC MODULATION OF CELL FUNCTION
In some aspects, a stent system including a support structure having first and second ends, comprising one or more members defining interior and peripheral regions for the structure, a lattice interfaced with the support structure, at least one transducer attached to the lattice, one or more leads electrically connected to the at least one transducer, and a power source connected to the one or more lead wires. In other aspects, a method for spatiotemporal control or expression of genes of one or more cells.

US2023340534 -- SONOGENETIC STIMULATION OF CELLS EXPRESSING A HETEROLOGOUS MECHANOSENSITIVE PROTEIN
Provided and described are mechanosensory polypeptides and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity and/or function of various types of cells that express the exogenous mechanosensory polypeptides using ultrasound.

US2023340408 -- SONOGENETIC MODULATION OF CELLS EXPRESSING BACTERIALLY-DERIVED MECHANOSENSITIVE PROTEINS
Provided and described are bacterial mechanosensory polypeptide and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity or function of various types of cells, including neurons, which express exogenous bacterial mechanosensory polypeptides, using ultrasound.

US2023263891 -- SONOGENETIC STIMULATION OF CELLS EXPRESSING TRPA1
Described herein are compositions featuring TRPA1 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRPA1 polypeptide in neurons and other cell types using ultrasound.