Li Hong-Hua, Zhang Su-Ming, Fang Si-Yu, Chen Chun-Lian, Luo Yun-Da, Guan Yang, Wang Dao-Wen, Xiao Xiao
Department of Neurology and Gene Therapy Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030 China.
Zhonghua Yi Xue Za Zhi. 2003 Sep 10;83(17):1513-6.
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.
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.
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.
We have demonstrated the effectiveness of rAAVSMCKA3999 in correcting pathology changes of skeletal muscle, which offer a promising avenue for DMD gene therapy.
杜氏肌营养不良症（DMD）是最常见且致命的遗传性骨骼肌疾病，由肌营养不良蛋白基因的隐性突变引起，目前尚无有效治疗方法。本文旨在研究重组腺相关病毒载体（rAAV）介导的肌营养不良蛋白小基因SMCKA3999能否有效改善mdx模型小鼠的营养不良病理状况。
我们使用肌营养不良蛋白小基因SMCKA3999构建rAAVSMCKA3999。将其注射到mdx小鼠（DMD模型）的骨骼肌中后，采用免疫荧光（IF）染色、伊文思蓝和电子显微镜等方法，观察rAAVSMCKA3999能否有效改善mdx模型小鼠的营养不良病理状况。
rAAVSMCK3999能在质膜上高效稳定地表达并恢复缺失的肌营养不良蛋白。rAAVSMCKA3999还能保护肌纤维膜的完整性。我们首次证明rAAVSMCKA3999可改善DMD的超微结构变化。
我们已证明rAAVSMCKA3999在纠正骨骼肌病理变化方面的有效性，这为DMD基因治疗提供了一条有前景的途径。
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