重组腺相关病毒载体介导的小基因SMCKA3999治疗对Duchenne肌营养不良肌力的影响

Recombinant adeno-associated virus vector-mediated minidystrophin gene SMCKA3999 improves dystrophic muscle contractile function in mdx mice

目的研究重组腺相关病毒载体(rAAV)介导的人dystrophin小基因SMCKA3999对DMD病理、肌力改变的治疗作用。方法将dystrophin小基因SMCKA3999克隆至rAAV并包装成rAAVSMC-KA3999病毒,以5×109病毒颗粒多点注射于DMD模型鼠mdx腓肠肌,基因治疗4月后免疫荧光法检测肌膜dystrophin基因表达,治疗5月后采用肌肉离体灌注电刺激测定腓肠肌肌力,观察rAAVSMCKA3999对mdx鼠肌力的疗效。结果rAAVSMCKA3999有效稳定表达并使肌膜缺失的dystrophin恢复,明显改善mdx鼠肌力。结论rAAVSMCKA3999对DMD治疗有效,能显著改善mdx鼠肌肉功能,应用重组腺相关病毒载体介导的dystrophin小基因SMCKA3999是治疗DMD有希望的方法。

Objective The aim is to study if adeno-associated virus vector-mediated minidystrophin gene SMCKA3999 can improve dystrophic muscle contractile function in mdx mice. Methods We used dystrophin minigene SMCIKA3999 to construct rAAV vectors, then rAAVSMCKA3999 was injected into the muscle of mdx mice （DMD model）. After four monthes the muscle contractile function was examined in mdx mice after five monthes. Results rAAVSMCK3999 resulted in efficient and stable expression and restoring the missing dystrophin onto the plasma membrane. At the same time we had demonstrated the improvement of dystrophic muscle contractile function in mdx mice. Conclusions We have demonstrated the effectiveness of rAAVSMCKA3999, offering a promising avenue for DMD gene therapy.