Gene Editing for Duchenne Muscular Dystrophy: From Experimental Models to Emerging Therapies.

Abstract

The CRISPR system has emerged as a ground-breaking gene-editing tool, offering promising therapeutic potential for Duchenne muscular dystrophy (DMD), a severe genetic disorder affecting approximately 1 in 5000 male births globally. DMD is caused by mutations in the dystrophin gene, which encodes a critical membrane-associated protein essential for maintaining muscle structure, function and repair. Patients with DMD experience progressive muscle degeneration, loss of ambulation, respiratory insufficiency, and cardiac failure, with most succumbing to the disease by their third decade of life. Despite the well-characterized genetic basis of DMD, curative treatments- such as exon skipping therapies, micro-dystrophin, and steroids- remain elusive. Recent preclinical studies have demonstrated the promise of CRISPR-based approaches in restoring dystrophin expression across various models, including human cells, murine systems, and large animal models. These advancements highlight the potential of gene editing to fundamentally alter the trajectory of the disease. However, significant challenges persist, including immunogenicity, off-target effects, and limited editing efficiency, which hinder clinical translation. This review provides a comprehensive analysis of the latest developments in CRISPR-based therapeutic strategies for DMD. It emphasizes the need for further innovation in gene-editing technologies, delivery systems, and rigorous safety evaluations to overcome current barriers and harness the full potential of CRISPR/Cas as a durable and effective treatment for DMD.