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Targeted gene delivery to nociceptors

Award Number: F32DE035781
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/12/2026
PERIOD OF PERFORMANCE END DATE: 09/11/2027

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Targeted gene delivery to nociceptors - PROJECT SUMMARY/ABSTRACT Chronic pain presents as a significant source of disability for large numbers of people in the U.S. Of these patients, many suffer from chronic craniofacial and dental pain which is caused by the continuous activation of trigeminal pain sensing neurons (nociceptors). Conditions like trigeminal neuralgia, for instance, are associated with significant morbidity and higher suicide rates. In addition, the current treatments for such persistent pain are limited and often come with debilitating side effects due to their off-target effects. This proposal aims to address this issue by developing an innovative gene therapy strategy designed to selectively silence trigeminal nociceptors while sparing other cell types in the peripheral and central nervous systems. Viral gene therapy is particularly promising for treating intractable craniofacial and dental pain, as it can be administered locally in a single dose to the affected nerve or ganglia, avoiding systemic distribution. Additionally, viral gene therapies are well-positioned for clinical translation, with several already approved by the FDA and many others in trials for neurological disorders. However, current viral vectors lack the ability to distinguish between sensory neuron subtypes, limiting their effectiveness for treating pain. To overcome this, we propose using recent breakthroughs in single-cell transcriptomics and epigenomics to identify cis regulatory elements, such as gene enhancers, that can drive viral gene expression specifically in trigeminal nociceptors. This proposal outlines two specific aims: 1) Identifying gene enhancers uniquely active in trigeminal ganglion nociceptors, and 2) Functionally screening AAVs (adeno-associated viruses) designed for trigeminal nociceptor specificity. In the first aim, we will perform single-cell epigenomic profiling of trigeminal ganglia from mice and humans to prioritize putative enhancers that regulate nociceptor-specific gene expression across species. In the second aim, we will create a library of viruses where each candidate enhancer drives expression of a unique molecular barcode, followed by in vivo screening using single-nucleus RNA sequencing to identify barcodes expressed primarily in trigeminal nociceptors. Successful completion of this project will produce nociceptor-specific viral tools for pain research. We also anticipate that these enhancers, which would be conserved across species, will enable similar cell-type specificity in humans. Ultimately, these vectors can be engineered to express inhibitory ion channels (e.g., chemogenetic or optogenetic), offering researchers and patients a non-opioid, on-demand solution for craniofacial and dental pain relief.


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: 2026 ( Subtotal = $80,352 )
2026	2026	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	3/19/2026	NEW	$80,352
														Subtotal = $80,352

Grand Total All Awards = $80,352

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Targeted gene delivery to nociceptors

Award Number: F32DE035781

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/12/2026

PERIOD OF PERFORMANCE END DATE: 09/11/2027

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