[Adeno-associated virus vector carrying human minidystrophin gene SMCKA3999 effectively ameliorates dystrophic pathology in mdx model mice].
OBJECTIVE
Duchenne muscular dystrophy (DMD) is the most common and letal genetic skeletal muscle disorder, caused by recessive mutations in the dystrophin gene and no treatment is available. The present paper is aimed to study if recombinant adeno-associated virus vector (rAAV) mediated dystrophin minigene SMCKA3999 could effectively ameliorates dystrophic pathology in mdx model mice.


METHODS
We used dystrophin minigene SMCKA3999 to construct rAAVSMCKA3999. When injected into the skeletal muscle of mdx mice (DMD model), we adopted methods of immunofluorescent (IF) staining, Evans Blue and electromicroscopy to observe if rAAVSMCKA3999 could effectively ameliorates dystrophic pathology in mdx model mice.


RESULTS
rAAVSMCK3999 resulted in efficient and stable expression and restoration of the missing dystrophin onto the plasma membrane. rAAVSMCKA3999 can also protect myofiber membrane integrity. For the first time we prove that rAAVSMCKA3999 can improve ultrastructure changes of DMD.


CONCLUSIONS
We have demonstrated the effectiveness of rAAVSMCKA3999 in correcting pathology changes of skeletal muscle, which offer a promising avenue for DMD gene therapy.
Li
Hong-Hua
HH
Department of Neurology and Gene Therapy Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030 China.
Zhang
Su-Ming
SM
Fang
Si-Yu
SY
Chen
Chun-Lian
CL
Luo
Yun-Da
YD
Guan
Yang
Y
Wang
Dao-Wen
DW
Xiao
Xiao
X
D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D016189:Dystrophin / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000628:therapy*
D016189:Dystrophin