# Next Generation Gene Therapy for Refractory Pain

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $688,317

## Abstract

Project Summary
Chronic pain affects over 25 million adults in the United States and is a major cause of disability. Currently
available pain treatments such as opioids are often ineffective and associated with unacceptable side effects
including respiratory depression and addiction. A major goal for new pain therapeutics is to inhibit the sensory
neurons which transmit pain signals (nociceptors) selectively without affecting other neurons involved in
innocuous sensation or the central nervous system. However, nociceptor-specific therapeutic approaches
remain in their infancy. Viral-based gene therapy offers several attractive advantages in treating refractory pain,
as viruses can be engineered to deliver a wide range of molecules, can be administered locally or systemically,
and have been recently approved by the Food and Drug Administration for a number of indications. However,
nociceptor-specific viral tools do not presently exist in large part due to the extraordinary heterogeneity of sensory
neurons that has made it difficult to identify molecular features that are unique to these cells. Recent advances
in single-cell genomics have enabled us to generate a cell atlas that describes the genes that are selectively
expressed in mouse and human nociceptors. This proposal aims to uncover the endogenous gene regulatory
elements that mediate nociceptor-specific gene expression patterns and engineer these elements into barcoded
adeno-associated viral libraries. To accomplish this, we propose the following specific aims: 1) Mapping
nociceptor-specific gene regulatory elements in mouse and human and 2) Generation of a nociceptor-specific
AAV toolkit. The nociceptor-specific viruses we develop in this proposal will be immediately useful to the scientific
community for accessing nociceptors in wild-type mice and likely other species. In addition, because we will
prioritize gene regulatory elements that are conserved between mouse and human nociceptors, we are optimistic
that the viruses we screen in mice will also drive nociceptor-specific gene expression in humans. These next
generation nociceptor-specific gene therapies would be ideally suited for treating certain refractory pain disorders
because they can be administered locally to neuropathic sensory ganglia through standard outpatient procedures
and can be engineered to drive expression of ion channels that silence nociceptor activity only in the presence
of a specific drug (chemogenetics). This opioid-free approach could have significant translational applications
for patients with refractory chronic pain who often have no other options for relief.

## Key facts

- **NIH application ID:** 10809576
- **Project number:** 5R01NS119476-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** William Russell Renthal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $688,317
- **Award type:** 5
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809576

## Citation

> US National Institutes of Health, RePORTER application 10809576, Next Generation Gene Therapy for Refractory Pain (5R01NS119476-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10809576. Licensed CC0.

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