# Project 3: Therapeutic Gene Editing for Huntington's Disease

> **NIH NIH U19** · JACKSON LABORATORY · 2024 · $667,843

## Abstract

PROJECT SUMMARY PROJECT 3 (HD)
Huntington Disease (HD) is an autosomal dominant disorder characterized by the loss of striatal neurons in the
central nervous system and is associated with progressive unwanted choreatic movements, behavioral and
psychiatric disturbances, and dementia1,2. HD is caused by CAG triplet repeat expansions in the first exon of
the HTT gene which codes for huntingtin protein, resulting in an expanded stretch of glutamines (polyQ). HD
affects all ethnic groups with an average incidence of ~5 per 100,000 people, though the prevalence can vary
by ~10 fold among populations. There is currently no cure or effective treatment for HD and while some
therapeutic interventions may lessen the severity of patient symptoms, HD typically results in fatality within 10-
30 years of disease onset.
In this follower project, we aim to improve HD protein expression to enable rescue of disease progression in HD
patients. Specifically, we aim to: (1) Optimize base editing and prime editing strategies to correct HD repeat
expansion; (2) Optimize AAV delivery for base and prime editor-mediated correction of the HD expansion in
mice; (3) Conduct pre-clinical studies at scale (JAX). We will work closely with the Gene Editing Core to develop
the latest base editing and/or prime editing technologies in HD model systems. We will iterate with the Gene
Editing Core to ensure that our genome editing tools maximize on-target editing efficiencies, minimize
undesirable gene editing byproducts and off-target editing events, and maximize compatibility with in vivo
delivery methods of potential therapeutic relevance.

## Key facts

- **NIH application ID:** 10842416
- **Project number:** 5U19NS132304-02
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** DAVID R LIU
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $667,843
- **Award type:** 5
- **Project period:** 2023-05-16 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842416

## Citation

> US National Institutes of Health, RePORTER application 10842416, Project 3: Therapeutic Gene Editing for Huntington's Disease (5U19NS132304-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842416. Licensed CC0.

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