# New classes of optogenetic and chemogenetic tools with a feedback control

> **NIH NIH DP2** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $1,350,000

## Abstract

New classes of optogenetic and chemogenetic tools with a feedback control
Project Summary
 Optogenetic and chemogenetic tools have revolutionized neuroscience research. They also hold great
promise for gene therapy of neurological disorders, such as epilepsy, schizophrenia and anxiety disorders.
For example, among the ~ 65 million people worldwide affected by epilepsy, 30% of them are resistant to
current medicine but could significantly benefit from new therapies that can quickly and effectively suppress
the irregular neuronal activities during seizures. However, we currently lack tools for prolonged neuronal
silencing with fast response to precisely modulate the irregular neuronal activities in neurological disorders
for both neuroscience research and therapeutic development. The state-of-the-art optogenetic tools for
neuromodulation provide fast temporal control via light, but they are limited by light-induced tissue heating in
long-lasting neuronal silencing experiments. Existing chemogenetic tools are effective for long-term neuronal
silencing, however, they are limited by their slow on/off rate due to drug administration. There is a need of
new tools that will enable prolonged neuronal silencing in quick response to the irregular neuronal activities
in neurological disorders. Our long-term goal is to engineer modular biological designs for controlling the
activities of specific neuronal pathways with tunable temporal control and minimal invasiveness for
neuroscience research and potential therapeutics. In this application, we propose to design the first closed-
loop chemogenetic tool with a feedback control to suppress the irregularly-high neuronal activities, and a
highly-light-sensitive optogenetic tool to achieve long-lasting silencing of neuronal activities. These new tools
based on membrane-tethered temporally-gated peptide agonists for G-protein-coupled receptors are highly
innovative and modular, and will open up a new frontier in designing neuromodulation tools for manipulating
neuronal pathways. They will also advance the basic research on neuronal circuitry and facilitate the
development of potential therapeutics for manipulating neuronal pathways in patients with neurological
disorders.

## Key facts

- **NIH application ID:** 10469777
- **Project number:** 1DP2MH132939-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Wenjing Wang
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,350,000
- **Award type:** 1
- **Project period:** 2022-08-15 → 2025-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469777

## Citation

> US National Institutes of Health, RePORTER application 10469777, New classes of optogenetic and chemogenetic tools with a feedback control (1DP2MH132939-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10469777. Licensed CC0.

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