# LEAD PROJECT 1: PHENYLKETONURIA (PKU)

> **NIH NIH U19** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $1,419,953

## Abstract

PROJECT SUMMARY
Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the gene encoding
phenylalanine hydroxylase (PAH), resulting in the accumulation of phenylalanine (Phe) to neurotoxic levels.
Among the five most frequently occurring pathogenic PAH variants worldwide is the c.842C>T (P281L) mutation,
which is amenable to adenine base editing. The current treatment options have significant limitations—a strict
low-Phe diet to which many patients find it difficult to adhere, and a daily injectable enzyme therapy with a
substantial risk of anaphylaxis. Lead Project 1 will focus on a lipid nanoparticle (LNP)-based adenine base
editing treatment for PKU in patients with the P281L variant, with the aim to file an IND application by the end
of the five-year funding period and begin a phase 1/2 clinical trial soon afterwards.

## Key facts

- **NIH application ID:** 10896260
- **Project number:** 5U19NS132301-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Kiran Musunuru
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,419,953
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896260

## Citation

> US National Institutes of Health, RePORTER application 10896260, LEAD PROJECT 1: PHENYLKETONURIA (PKU) (5U19NS132301-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10896260. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*