source: Molecular Therapy: The Journal of The American Society of Gene Therapy
Davies KE, Guiraud S
Systemic delivery of genes to muscle using vectors based on recombinant adenovirus-associated virus (rAAV) has been explored extensively in animal models of Duchene muscular dystrophy (DMD) to replace the missing dystrophin gene in both skeletal and cardiac muscles. A major challenge in bringing this approach to the clinic for DMD is the low gene capacity of rAAV (∼5 kb) and the large size of the dystrophin mRNA (14 kb).
Although dystrophin mini-genes and micro-genes were reported almost three decades ago, many lacked important binding sites of the protein. In this issue of Molecular Therapy, Ramos et al. report the functional evaluation of eight different micro-dystrophin genes whose function is optimized by varying the rod domain structure of dystrophin. This work is significant because, although these dystrophin micro-genes are not fully functional, they are showing sufficient promise to be included in clinical trials in DMD patients.
University of Oxford, UK
10.1016/j.ymthe.2019.01.019 read more