# Genome editing for the correction of Pompe disease

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $172,089

## Abstract

Pompe disease is a potentially fatal metabolic myopathy caused by the deficiency of lysosomal acid α-
glucosidase (GAA; EC 3.2.1.20) that leads to accumulation of lysosomal glycogen and muscle damage. The
only currently available treatment consists of enzyme replacement therapy (ERT) with recombinant human
GAA, which requires frequent treatments with high lifetime costs. Genome editing in Pompe disease,
conversely, could permanently correct mutations in the GAA gene and ameliorate patient symptoms. The
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system has emerged as a
promising tool to edit genomes with high precision. However, previous studies that used this system for
mutation correction through homologous recombination required the transduction of each cell with two adeno-
associated virus (AAV) vectors with relatively low efficiency, in comparison with using a single AAV vector as
proposed here. Given that AAV vectors do not uniformly transduce muscle, the efficiency with which two
vectors transduce individual muscle cells is low; therefore, the application of this technology to correct
mutations in Pompe disease has not been possible. We propose to develop a genome editing system using a
single AAV vector to correct the biochemical abnormalities and muscle weakness in Pompe disease. We will
correct two of the most common GAA gene variants. Genome editing in Pompe disease will permanently
correct GAA and continuously express GAA ameliorating patient symptoms and represents a major
advancement for the treatment of Pompe patients.

## Key facts

- **NIH application ID:** 10071111
- **Project number:** 1R21AR073470-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Dwight D Koeberl
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,089
- **Award type:** 1
- **Project period:** 2020-07-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071111

## Citation

> US National Institutes of Health, RePORTER application 10071111, Genome editing for the correction of Pompe disease (1R21AR073470-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071111. Licensed CC0.

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