Friday, August 15, 2025 8/15/2025

Sonogenetic Remote Control of Cellular Function

Award Number: DP1EB033154
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Sonogenetic Remote Control of Cellular Function - SUMMARY The discovery and development of fluorescent proteins and optogenetics revolutionized biology by making it possible to image and control specific cellular processes with visible light. While these tools have enabled countless biological discoveries, the poor penetration of light into living tissue makes it difficult to use optical techniques in intact animals. As a result, biological phenomena ranging from the signaling of neurons in deep- brain regions, to the infiltration of immune cells into tumors, to the microbial colonization of the GI tract, are challenging to study within their natural in vivo context. If instead of light it were possible to visualize and manipulate cellular function using a more penetrant form of energy such as ultrasound, this would open previously inaccessible domains of in vivo biology to direct investigation. In addition, it would enhance the development of cell-based therapies by allowing cellular agents to be seen and controlled after administration into the human body. The physics of ultrasound make it an ideal modality for deep-tissue cellular communication. Sound waves in the MHz range are weakly scattered by tissue and can therefore penetrate several cm into the body. With wavelengths on the order of 100 µm and travel times < 1 ms, ultrasound can access many key structures and processes. When focused, sound waves can deliver mechanical and thermal energy to precise anatomical locations. These properties have already made ultrasound one of the world’s most widely used technologies for medical imaging and non-invasive surgery. However, the potential of ultrasound to serve as a tool for cellular imaging and control has been relatively untapped due to a lack of methods to connect it to the function of specific cells and biomolecules. In previous work, the Shapiro lab has pioneered the use of ultrasound in cellular and molecular imaging by developing the first acoustic reporter genes and biosensors for ultrasound, aiming to “do for ultrasound what fluorescent proteins have done for fluorescence microscopy”. The major goal of our proposed new research direction is to “do for ultrasound what optogenetics has done for light” by giving sound waves the ability to control specific cellular functions such as neuronal excitation, gene expression and intracellular signaling in vivo. The basic principle of our approach is to (1) use focused ultrasound to deposit acoustic energy at a specific location in tissue, (2) use genetically encoded “acoustic antennae” to convert this energy into local mechanical force, and (3) use this force to actuate mechanosensitive receptors to produce specific cellular signals. We will implement this approach in neurons and immune cells to enable unique neuroscience and cell therapy applications. If successful, this work will help establish the new field of sonogenetics by providing researchers and clinicians with the unprecedented ability to “point and click” on cells deep within the body and tell them what to do.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,172,500 )
2025	2025	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	5	7/3/2025	NON-COMPETING CONTINUATION	$1,172,500
														Subtotal = $1,172,500

Issue Date FY: 2024 ( Subtotal = $1,172,500 )
2024	2024	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	4	7/29/2024	NON-COMPETING CONTINUATION	$1,172,500
														Subtotal = $1,172,500

Issue Date FY: 2023 ( Subtotal = $1,172,500 )
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	3	8/1/2023	NON-COMPETING CONTINUATION	$1,172,500
														Subtotal = $1,172,500

Issue Date FY: 2022 ( Subtotal = $1,172,500 )
2022	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	2	8/3/2022	NON-COMPETING CONTINUATION	$1,172,500
														Subtotal = $1,172,500

Issue Date FY: 2021 ( Subtotal = $1,172,500 )
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Trans-NIH Research Support	000	1	9/13/2021	NEW	$1,172,500
														Subtotal = $1,172,500

Grand Total All Awards = $5,862,500

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Sonogenetic Remote Control of Cellular Function

Award Number: DP1EB033154

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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