Dystrophin (DMD) (DMD)

The human dystrophin (DMD) gene is the largest known gene in the human genome, encoding a critical protein that maintains the structural integrity of cardiac and skeletal muscle fibers (NCBI Gene ID: 1756). Dystrophin acts as a molecular shock absorber, linking the intracellular actin cytoskeleton to the extracellular matrix via the dystrophin-associated glycoprotein complex (UniProt: P11532). Mutations in this gene, typically large deletions or duplications that disrupt the open reading frame, result in Duchenne muscular dystrophy (DMD), a severe, progressive muscle-wasting disease (StatPearls: Duchenne Muscular Dystrophy). The use of CRISPR/Cas ribonucleoprotein (RNP) complexes represents a precision medicine approach to treat DMD by directly editing the genome to restore the reading frame or correct specific mutations (Nature Communications, 2019). Unlike viral-mediated gene therapy, RNP delivery offers a transient presence of the editing machinery, potentially reducing the risk of off-target effects and long-term immune responses to the Cas9 enzyme (Science Advances, 2017). This approach is particularly advantageous for targeting the DMD gene's massive size, which exceeds the packaging capacity of standard viral vectors like AAV (Molecular Therapy, 2017). Therapeutic development focuses on optimizing delivery to systemic muscle tissues and ensuring high-fidelity editing to restore functional dystrophin protein levels (Journal of Clinical Investigation, 2019).

Other names

DMD geneDystrophinMuscular dystrophy, Duchenne and Becker typesDystrophin-associated glycoprotein complex

The CRISPR/Cas9 RNP complex targets specific sequences within the DMD gene to induce double-strand breaks, facilitating either non-homologous end joining (NHEJ) to skip mutated exons or homology-directed repair (HDR) to correct mutations, thereby restoring the production of functional dystrophin protein (Nature Communications, 2019).