# PROJECT 2: HEREDITARY TYROSINEMIA TYPE 1 (HT1)

> **NIH NIH U19** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $1,630,863

## Abstract

PROJECT SUMMARY
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive metabolic liver disease that can cause death in
the first months of life and incurs an increased risk of hepatocellular cancer. The current treatment option—strict
adherence to twice daily dosing with NTBC, a repurposed herbicide that inhibits HPD—is limited by high
noncompliance rates. Liver transplant remains the only option for those patients that fail medical management.
Genome editing to inactivate the HPD gene in the tyrosine catabolic pathway provides a potential universal, one-
time, lifelong treatment for HT1 patients. Project 2 will focus on an LNP-based adenine base editing postnatal
treatment of HT1, with the aim to file an IND application and begin a clinical trial, and prenatal base editing
treatment of HT1, with the aim of performing preclinical studies during the five-year funding period to enable an
eventual IND application if the postnatal clinical trial proves successful.

## Key facts

- **NIH application ID:** 10896261
- **Project number:** 5U19NS132301-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** William H. Peranteau
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,630,863
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896261

## Citation

> US National Institutes of Health, RePORTER application 10896261, PROJECT 2: HEREDITARY TYROSINEMIA TYPE 1 (HT1) (5U19NS132301-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896261. Licensed CC0.

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