Public Release: 

DNA vaccine and gene therapy trials for muscular dystrophy

Proceedings of the National Academy of Sciences

A mouse study suggests that immunization with a DNA vaccine could help improve gene therapy trials for Duchenne muscular dystrophy (DMD). DMD is a potentially fatal, muscle-wasting genetic disorder that afflicts one out of 5,000 male children and stems from defects in the production of the protein dystrophin in skeletal and cardiac muscles. Gene therapy trials in which partial dystrophin gene sequences are ferried to muscle cells on an adeno-associated virus (AAV) have shown promise. However, such trials face numerous challenges, including the generation of an immune response in recipients against the restored dystrophin and AAV vehicle. To circumvent such immune responses, Lawrence Steinman and colleagues immunized a mouse model of DMD that lacks dystrophin with a DNA vaccine containing microdystrophin, which is around one-third the size of dystrophin but nonetheless restores some muscle function. One week after gene therapy, the authors injected the vaccine into the quadriceps of mice once weekly for 32 weeks. Gene therapy restored dystrophin production in all mice. Force generation in calf muscles was improved in immunized mice that received gene therapy, compared with mice that received gene therapy but were not immunized. More importantly, mice that received the vaccine for 32 weeks as well as gene therapy exhibited diminished antibody responses against 66 human dystrophin peptides in lab assays, compared with mice that received gene therapy alone. Immunization also appeared to reduce antibody responses against the AAV6 vehicle used for gene therapy. Follow-up studies over 60 weeks, when several DMD symptoms are heightened, are required to fully assess the vaccine's efficacy, but the findings suggest a potential approach to improve gene therapy trials for DMD, according to the authors.

Article #18-08648: "Engineered DNA plasmid reduces immunity to dystrophin while improving muscle force in a model of gene therapy of Duchenne dystrophy," by Peggy Ho et al.

MEDIA CONTACT: Lawrence Steinman, Stanford University School of Medicine, Stanford, CA; tel: 650-725-6401; e-mail:


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