To design a novel efficacious viral vector for treating Mucopolysaccharidosis Type VII (MPS VII) caused by a mutation in the gene ( allele). β-Glu expression of single-stranded () and self-complementary AAV () vectors are tested with cultured murine fibroblasts. The vector was chosen in further studies to prolong the life span and treat corneal pathology of mice via intrahepatic injection of neonates and intrastromal injection in adults, respectively. Corneal pathology was studied using HRT2 in vivo confocal microscope and histochemistry in mice corneas. Both and vectors expressed murine β-Glu in cultured fibroblasts. The vector had higher transduction efficiency than the vector. To prolong the life span of mice, neonates (3 days old) were administered with virus via intrahepatic injection. The treatment improves the survival rate of mice, prolonging the median survival rate from 22.5 weeks (untreated) to 50 weeks (treated). Thereafter, we determined the efficacy of the virus in ameliorating corneal cloudiness observed in aged mice. Both corneal cloudiness and stroma thickness decreased, and there was the presence of β-Glu enzyme activity in the corneas receiving virus associated with morphology change of amoeboid stromal cells in untreated to characteristic dendritic keratocytes morphology after 4–12 weeks of virus injection. Intrahepatic injection of is efficacious in prolonging the life span of mice, and intrastromal injection can ameliorate corneal phenotypes. Both strategies can be adapted for treating other MPS.

中文翻译：

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用于治疗粘多糖贮积症 VII 型 (MPS VII) 角膜混浊的自我补充 AAV 载体疗法

设计一种新型有效的病毒载体，用于治疗由基因（等位基因）突变引起的粘多糖贮积症 VII 型（MPS VII）。使用培养的鼠成纤维细胞测试单链 () 和自互补 AAV () 载体的 β-Glu 表达。在进一步的研究中选择该载体分别通过新生儿肝内注射和成人基质内注射来延长小鼠的寿命并治疗角膜病理。使用 HRT2 活体共聚焦显微镜和小鼠角膜组织化学研究角膜病理学。和载体均在培养的成纤维细胞中表达鼠β-Glu。该载体比普通载体具有更高的转导效率。为了延长小鼠的寿命，通过肝内注射给新生儿（3天大）注射病毒。该治疗提高了小鼠的存活率，将中位存活率从 22.5 周（未治疗）延长至 50 周（治疗）。此后，我们确定了该病毒在改善老年小鼠角膜混浊方面的功效。角膜混浊度和基质厚度均下降，并且在接受病毒的角膜中存在β-Glu酶活性，这与未经处理的变形虫基质细胞的形态变化有关，在病毒注射4​​-12周后，其特征性树突状角膜细胞形态发生变化。肝内注射可有效延长小鼠的寿命，基质内注射可改善角膜表型。这两种策略均可适用于治疗其他 MPS。