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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 To study the therapeutic effect of human dystrophin gene SMCKA3999 mediated by recombinant adeno-associated virus vector (rAAV) on pathological and muscular changes of DMD. Methods The dystrophin minigene SMCKA3999 was cloned into rAAV and packaged into rAAVSMC-KA3999 virus. The MDSCs were injected into mdx gastrocnemius muscle of DMD model rats with 5 × 109 virus particles. The expression of dystrophin gene in muscle was detected by immunofluorescence four months after gene therapy. Month after muscle stimulation by gastrocnemius muscle gastrocnemius muscle, observed rAAVSMCKA3999 mdx rat muscle strength. Results rAAVSMCKA3999 effective and stable expression of the absence of sarcomere dystrophin recovery, significantly improved mdx mouse muscle strength. Conclusion rAAVSMCKA3999 is effective in DMD treatment and can significantly improve the muscle function of mdx mice. It is a promising method to treat DMD with recombinant adeno-associated virus vector-mediated dystrophin minigene SMCKA3999.