# Sonogenetics 2.0

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $609,145

## Abstract

PROJECT SUMMARY/ABSTRACT
Achieving noninvasive, cell-type-specific, and spatially precise neuromodulation remains to be a major
challenge in the development of neuromodulation technologies. The objective of this project is to develop
Sonogenetics 2.0, the next-generation sonogenetic technique for cell-type-specific, spatially precise
neuromodulation in the whole brain of freely behaving animals without intracranial surgery. Sonogenetics 2.0
employs low-intensity focused ultrasound (FUS) combined with microbubbles to deliver intranasally administered
adeno-associated viruses (AAVs) to the FUS-targeted brain region with minimal systemic exposure. It then
utilizes FUS sonication to remotely activate the expressed ultrasound-sensitive ion channels encoded by the
AAVs and thereby controls the activity of AAV-transduced neurons. Sonogenetics 2.0 addresses three critical
barriers to developing sonogenetics: the lacks molecular probes with optimized ultrasound sensitivity (Aim 1),
requires surgical injection of viral vectors to express the probes (Aim 2), and has a low spatial resolution in
delivering ultrasound in the mouse brain (Aim 3). Sonogenetics 2.0 will be independently validated by
neuroscience laboratories and benchmarked with optogenetics (Aim 4). The proposed Sonogenetics 2.0 is
significant because technological breakthroughs are urgently needed to fulfill the great potential of
sonogenetics. Sonogenetics 2.0 provides a complementary tool to existing neuromodulation techniques with the
potential to be translated to large animals and humans. A multidisciplinary team with combined expertise in
ultrasound device design, ion channel engineering, neuromodulation, and neuroscience is well suited to this
project. This project is innovative because Sonogenetics 2.0 is the first-in-class ultrasound tool for completely
noninvasive and cell-type-specific neuromodulation by combining noninvasive genetic construct delivery with
noninvasive activation of transduced neurons. The proposed research is expected to have a sustained, powerful
impact in the research field of sonogenetics and provide the neuroscience community with a transformative tool
that can be widely used to advance our current capabilities in investigating cell-type-specific processes in intact
mammalian brains.

## Key facts

- **NIH application ID:** 10881982
- **Project number:** 5R01NS128461-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Hong Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $609,145
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881982

## Citation

> US National Institutes of Health, RePORTER application 10881982, Sonogenetics 2.0 (5R01NS128461-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10881982. Licensed CC0.

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