# Non-Invasive and Non-Viral Sono-Optogenetics

> **NIH NIH R35** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $396,250

## Abstract

Project Abstract
Over the past decade, optogenetics has increasingly become an important technology for spatiotemporal control
of neural activity, cardio functions, muscle cell activity, protein-protein interaction, and disease applications,
through the genetically encoded light-activated proteins. However, there are still two major challenges of this
technology: 1.the delivery of light to into deep body areas such as brain or heart generally requires the optical
fiber implantation which could result in damage of cells and tissue. 2. Gene expression requires viral transduction,
which suffer from a number of limitations such as the host immune response, the stability expressed proteins
over time, the limitations on maximum gene size and the lack of economic scalability for manufacture. To address
the first challenge, we recently developed a technology named ‘sono-optogenetics’ to convert focused ultrasound
(FUS) to light for non-invasive optogenetics. The nanoparticles are injected into the circulating blood so that
neither craniotomy nor intracranial implantation is required for achieving optogenetics. However, these inorganic
nanoparticles are generally difficult to be modified to emit different colors of light for multiplex optogenetic control
and are not biodegradable after accumulating in the animal livers after use, causing long-term safety concerns.
Therefore, the goal of this proposal and the focus of my research lab, is to tackle the remaining challenges for
optogenetics through designing organic nanomaterials, including hydrogen-bonded organic frameworks
nanoparticles, chemical assembly of DNA plasmids and cationic polymer delivery agents. Specifically, we are
planning to 1) design biodegradable nanoparticles to convert ultrasound to light for multi-colored sono-
optogenetics. 2) improve the delivery of plasmid DNAs through nucleopore through covalent chemical assembly
strategies and 3) design advanced cationic polymers for improving endosome escape, cellular uptake and
diffusivity through extracellular space in non-viral gene delivery. The work will also enhance our understanding
the transport and interaction of organic nanoparticles in cells. As a result, I believe that the proposed works is
well suited for the NIH R35 Maximizing Investigators’ Research Award.

## Key facts

- **NIH application ID:** 10501831
- **Project number:** 1R35GM147408-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Huiliang Wang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,250
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501831

## Citation

> US National Institutes of Health, RePORTER application 10501831, Non-Invasive and Non-Viral Sono-Optogenetics (1R35GM147408-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10501831. Licensed CC0.

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