Duchenne muscular dystrophy treatment with lentiviral vector containing mini-dystrophin gene in vivo.

Duchenne muscular dystrophy (DMD) is an incurable X-linked recessive genetic disease caused by mutations in the dystrophin gene. Many researchers aim to restore truncated dystrophin via viral vectors. However, the low packaging capacity and immunogenicity of vectors have hampered their clinical application. Herein, we constructed four lentiviral vectors with truncated and sequence-optimized dystrophin genes driven by muscle-specific promoters. The four lentiviral vectors stably expressed mini-dystrophin in C2C12 muscle cells in vitro. To estimate the treatment effect in vivo, we transferred the lentiviral vectors into neonatal C57BL/10ScSn-Dmdmdx mice through local injection. The levels of modified dystrophin expression increased, and their distribution was also restored in treated mice. At the same time, they exhibited the restoration of pull force and a decrease in the number of mononuclear cells. The remissions lasted 3-6 months in vivo. Moreover, no integration sites of vectors were distributed into the oncogenes. In summary, this study preliminarily demonstrated the feasibility and safety of lentiviral vectors with mini-dystrophin for DMD gene therapy and provided a new strategy to restore truncated dystrophin.