Cassandra Gorsuch, PhD, on the Durability and Next Steps for the ARCUS Gene Editing Platform in DMD

This video originally appeared on our sister site, NeurologyLive®.

"With ARCUS, once the edit happens, it’s permanent—designed to outlast the vector and deliver a long-term, meaningful benefit for patients."

A severe X-linked disorder caused by mutations in the DMD gene, Duchenne muscular dystrophy (DMD) results in nonfunctional or absent dystrophin and progressive muscle degeneration. Typically, patients with the disease die in early adulthood. The therapeutic approaches currently available for the disorder, including gene therapies that deliver truncated, synthetic dystrophin constructs, have demonstrated only modest clinical benefit, and furthermore, in pediatric populations in particular may be held back by concerns related to durability. As such, the field has continued innovation with the exploration of gene editing approaches. One such example is Precision Biosciences' ARCUS-mediated gene editing platform.

By using 2 ARCUS nucleases, delivered using a single adeno-associated virus (AAV), to excise exons 45-55 of the dystrophin gene, this new approach is intended to bring about restoration of native dystrophin function. At the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific conference, held March 16-19, in Dallas, Texas, preclinical data presented by the company demonstrated significant improvement of maximum force output (MFO) after ARCUS treatment, reaching 89% of the MFO levels seen in nondiseased mice. The data also showed significant resistance to eccentric injury, reaching a 66% improvement compared with disease untreated mice.

At the conference, CGTLive®'s sister site NeurologyLive® interviewed Cassandra Gorsuch, PhD, the chief scientific officer at Precision, about the company’s strategy in bringing this gene editing platform into clinical trials. She emphasized the approach’s durability, noting that once ARCUS edits the dystrophin gene, the change is permanent—even if the AAV delivery vector is later silenced or lost. Furthermore, Gorsuch highlighted the platform’s functional benefits, including its targeted exon 45-55 deletion strategy and potential to correct satellite stem cells for lasting effect.

Click here for more MDA 2025 coverage.

REFERENCE
1. Mischler A, Owens G, Lewis W, et al. ARCUS-Mediated Excision of Exons 45-55 Leads to Functional Del45-55 Dystrophin and Restoration of Skeletal Muscle-Function for the Treatment of DMD. Presented at: 2025 MDA Clinical & Scientific conference; March 16-19; Dallas, TX. ABSTRACT 0159