# Acoustothermogenetics for Cell Engineering

> **NIH NIH R35** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $537,740

## Abstract

Abstract
Fluorescent proteins (FPs) and their derived biosensors based on fluorescence resonance energy
transfer (FRET) have revolutionized biology/medicine by allowing the visualization of dynamic molecular
activities in live cells with high spatiotemporal resolutions. Optogenetics has enabled the perturbation of
specific molecular events in living systems, however, there is a lack of methods to manipulate cells and
tissues deep in the body. I propose here to develop acoustothermogenetics as a general method to allow
the direct, remotely-controlled, non-invasive manipulation of live cell functions in deep body sites for the
correction of pathological processes and the control of specific therapeutic interventions. I will first
engineer molecular sensors and genetic transducers which will allow the engineered cell to perceive the
ultrasound signals directly and transduce them into genetic activation for the production of desired protein
regulators. I will then use cell-based immunotherapy, particularly chimeric antigen receptor (CAR)-
expressing T cells, as my initial test target to establish, in principle, the practical utility of this new method.
CAR-T immunotherapy is becoming a paradigm-shifting therapeutic approach for cancer treatment, but
its broad application has major challenges. I propose to develop ultrasound-sensitive CAR-T cells for
their control from a distance by ultrasound transducers to target and eradicate solid tumors. Lastly, I will
extend this remotely-controlled acoustothermogenetics approach to develop a general system that would
allow the control of, in principle, any genetic or epigenetic modulation in live cells for the reprogramming
of cellular functions under in vivo situation. This approach should allow the remotely-controlled cell
activation with a high spatiotemporal precision in a non-invasive manner for a broad range of therapeutic
applications. This novel approach should also provide a general paradigm to dynamically control
molecular and cellular functions for biological studies and clinical applications.

## Key facts

- **NIH application ID:** 10631097
- **Project number:** 5R35GM140929-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Yingxiao Wang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $537,740
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10631097

## Citation

> US National Institutes of Health, RePORTER application 10631097, Acoustothermogenetics for Cell Engineering (5R35GM140929-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10631097. Licensed CC0.

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