Advancing Efficacy, Longevity, and Safety of Gene Editing Therapies for DMD
Abstract
Adeno-associated viral (AAV) vector-based gene therapies are generating encouraging results in Duchenne muscular dystrophy (DMD) trials. However, these approaches do not fully restore muscle function and therapeutic benefits may be lost over time due to muscle turnover following maintenance, or trauma. Gene editing (CRISPR) offers a promising alternative to correct dystrophin production from the patient’s own gene. Here, long-term therapeutic outcome could benefit from repairing mutations in both existing muscles and in muscle stem cells (SCs) to ensure that dystrophin continues to be produced in case of muscle injury and regeneration. While early studies have shown that muscle and SCs can be targeted with AAV-CRISPR, efficient and safe approaches for more straightforward clinical translation have yet to be demonstrated. Here we propose developing methods to permanently restore dystrophin expression in striated muscle by correcting DMD-causing mutations in both existing muscle and in SCs. We will also develop sensitive switches for turning gene editing On and Off, with the purpose of reduced risks of unintended editing or development of immune responses within treated patient muscles. Overall, these studies are designed to achieve significant long-term therapeutic improvements of DMD symptoms.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310575
Entities
People
- Niclas Bengtsson
Organizations
- United States Army
- University of Washington