# iSonogenetics for incisionless cell-type-specific neuromodulation of non-human primate brains

> **NIH NIH UG3** · WASHINGTON UNIVERSITY · 2021 · $715,574

## Abstract

PROJECT SUMMARY/ABSTRACT
Critical advances in the treatment of human brain disorders are hindered by our inability to specifically target
dysfunctional circuitry in a safe and noninvasive manner. Existing noninvasive techniques (e.g., transcranial
magnetic, electrical, and ultrasound neuromodulation) activate many brain circuit components within the targeted
region, and their efficacies are difficult to control. Genetic approaches (e.g., optogenetics and chemogenetics)
modulate defined neural populations, but commonly require invasive surgical procedures for intracranial injection
of viral vectors encoding stimulus-sensitive ion channels and/or implantation of long-term hardware for stimulus
delivery. The objective of this application is to develop and validate a next-generation neuromodulation tool,
incisionless sonogenetics (iSonogenetics), for noninvasive and cell-type-specific manipulation of neuronal
activity in non-human primate (NHP) brains. Our ultimate goal is to use iSonogenetics for the modulation of the
NHP and human brain to identify the neuronal bases of cognitive behavior and to progress toward the targeted
treatment of human brain disorders. iSonogenetics involves a dual approach. (1) Sonodelivery uses focused
ultrasound (FUS) to noninvasively deliver intranasally administered adeno-associated viruses (AAVs) encoding
a thermosensitive ion channel, transient receptor potential vanilloid 1 (TRPV1), to genetically defined populations
of neurons. (2) Sonoactivation uses FUS to induce mild warming, which opens TRPV1 channels and thereby
activates the AAV-transduced neurons. Guided by strong preliminary data obtained in rodents, our objective will
be accomplished by pursuing three specific aims: (1) Develop sonodelivery for noninvasive and efficient AAV
delivery to a targeted brain region with minimal systemic exposure in anesthetized NHPs; (2) Develop
sonoactivation for safe and reliable activation of AAV-transduced neurons in anesthetized NHPs; (3) Validate
iSonogenetics in awake NHPs by conducting behavior testing. The proposed iSonogenetics is innovative
because it can achieve noninvasive and cell-type-specific neuromodulation at deep brain targets with a high
spatiotemporal resolution. The proposed research is significant because it directly addresses the central goal
of RFA-MH-19-135 by providing the neuroscience community with a first-in-class neuromodulation tool that has
the potential to transform our approaches for probing cell-specific processes and uncover new ways to
understand and treat human brain disorders.

## Key facts

- **NIH application ID:** 10270569
- **Project number:** 1UG3MH126861-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Hong Chen
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $715,574
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10270569

## Citation

> US National Institutes of Health, RePORTER application 10270569, iSonogenetics for incisionless cell-type-specific neuromodulation of non-human primate brains (1UG3MH126861-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10270569. Licensed CC0.

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