Toward the correction of muscular dystrophy by gene editing

Abstract

Recent advances in gene editing technologies are enabling th potential correction of devastating monogenic disorders throug elimination of underlying genetic mutations. Duchenne muscula dystrophy (DMD) is an especially severe genetic disorder cause by mutations in the gene encoding dystrophin, a membrane associated protein required for maintenance of muscle structur and function. Patients with DMD succumb to loss of mobility earl in life, culminating in premature death from cardiac and respira tory failure. The disease has thus far defied all curative strategies CRISPR gene editing has provided new opportunities to ameliorat the disease by eliminating DMD mutations and thereby restor dystrophin expression throughout skeletal and cardiac muscle Proof-of-concept studies in rodents, large mammals, and huma cells have validated the potential of this approach, but numerou challenges remain to be addressed, including optimization of gen editing, delivery of gene editing components throughout th musculature, and mitigation of possible immune responses. Thi paper provides an overview of recent work from our laborator and others toward the genetic correction of DMD and consider the opportunities and challenges in the path to clinical translation Lessons learned from these studies will undoubtedly enabl further applications of gene editing to numerous other disease of muscle and other tissues.