Work

Engineered DNA plasmid reduces immunity to dystrophin while improving muscle force in a model of gene therapy of Duchenne dystrophy

Year: 2018

Type: article

Abstract: Significance Duchenne muscular dystrophy is a genetic disorder in which mutations in the dystrophin gene causes severe muscle wasting. A proposed treatment method involves systemic gene replacement therapy to introduce a functional dystrophin gene to the skeletal and cardiac muscles of the patient via rAAV6. A potentially serious problem may arise from immune recognition of dystrophin and the accompanying adeno-associated viral (AAV) vector. This unwanted immunity could interfere with successful long-term dystrophin expression by muscle cells. To suppress the unwanted immune response, a DNA vaccine was engineered to dampen immunity to both dystrophin and AAV6 capsid. Development of this engineered plasmid aims to improve gene replacement therapy and to overcome problems inherent with unwanted immunity to the encoded protein and to the delivery vector.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1808648115