Sci Rep. 2012;2:399. doi: 10.1038/srep00399. Epub 2012 May 8.
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Therapeutic gene replacement of a dystrophin cDNA into dystrophic muscle can provide functional dystrophin protein to the tissue. However, vector-mediated gene transfer is limited by anti-vector and anti-transgene host immunity that causes rejection of the therapeutic protein. We hypothesized that rapamycin (RAPA) would diminish immunity due to vector-delivered recombinant dystrophin in the adult mdx mouse model for DMD. To test this hypothesis, we injected limb muscle of mdx mice with RAPA-containing, poly-lactic-co-glycolic acid (PLGA) microparticles prior to dystrophin gene transfer and analyzed treated tissue after 6 weeks. RAPA decreased host immunity against vector-mediated dystrophin protein, as demonstrated by decreased cellular infiltrates and decreased anti-dystrophin antibody production. The interpretation of the effect of RAPA on recombinant dystrophin expression was complex because of an effect of PLGA microparticles.
杜氏肌营养不良症（DMD）是由肌营养不良蛋白基因突变引起的。将肌营养不良蛋白 cDNA 的治疗性基因替代到病变肌肉中，可以为组织提供功能性肌营养不良蛋白。然而，载体介导的基因转移受到抗载体和抗转基因宿主免疫的限制，导致治疗性蛋白被排斥。我们假设雷帕霉素（RAPA）会因载体递送的重组肌营养不良蛋白而减少成年 mdx 肌营养不良症小鼠模型中的免疫。为了验证这一假设，我们在肌营养不良蛋白基因转移之前，用含有雷帕霉素的聚乳酸-羟基乙酸共聚物（PLGA）微球注射 mdx 小鼠的四肢肌肉，并在 6 周后分析处理过的组织。雷帕霉素降低了宿主对载体介导的肌营养不良蛋白的免疫反应，表现为细胞浸润减少和抗肌营养不良蛋白抗体产生减少。雷帕霉素对重组肌营养不良蛋白表达的影响的解释很复杂，因为 PLGA 微球有影响。
