Why is gene therapy for Duchenne muscular dystrophy challenging?

Gene therapy for Duchenne muscular dystrophy (DMD) is exceptionally challenging primarily due to the nature of the DMD gene itself and the limitations of current delivery systems.1

• Gene Size: The DMD gene is one of the largest in the human genome, making it too massive to fit into standard viral vectors, such as the adeno-associated virus (AAV) capsids typically used to deliver genetic material into cells.1
• Delivery Constraints: Because AAV vectors have limited capacity, researchers must use a truncated version of the gene, known as "micro-dystrophin," which is only about one-third the size of the full-length protein. Consequently, this approach fails to include several important functional features of natural dystrophin.1
• Safety Risks: Clinical trials for gene therapy and gene editing have faced significant safety hurdles, including reports of patient deaths and immune responses to the viral vectors used for delivery.12

Developing effective treatments requires balancing these technical limitations with the ethical imperative to ensure patient safety, as researchers continue to explore alternatives like CRISPR and improved delivery methods.12