T cells are the current choice for many cell therapy applications. They are relatively easy to access, expand in culture, and genetically modify. Rapamycin-conditioning ex vivo reprograms T cells, increasing their memory properties and capacity for survival, while reducing inflammatory potential and the amount of preparative conditioning required for engraftment. Rapamycin-conditioned T cells have been tested in patients and deemed to be safe to administer in numerous settings, with reduced occurrence of infusion-related adverse events. We demonstrate that ex vivo lentivirus-modified, rapamycin-conditioned CD4+ T cells can also act as next-generation cellular delivery vehicles-that is, "micropharmacies"-to disseminate corrective enzymes for multiple lysosomal storage disorders. We evaluated the therapeutic potential of this treatment platform for Fabry, Gaucher, Farber, and Pompe diseases in vitro and in vivo. For example, such micropharmacies expressing α-galactosidase A for treatment of Fabry disease were transplanted in mice where they provided functional enzyme in key affected tissues such as kidney and heart, facilitating clearance of pathogenic substrate after a single administration.

中文翻译：

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用于溶酶体贮积症的自体、慢病毒修饰的 T-rapa 细胞“微药房”。


T 细胞是当前许多细胞治疗应用的选择。它们相对容易获得、在文化中扩展以及进行基因改造。雷帕霉素离体条件对 T 细胞进行重新编程，提高其记忆特性和生存能力，同时减少炎症潜力和植入所需的准备条件量。雷帕霉素条件化 T 细胞已在患者中进行了测试，并被认为在多种环境下使用是安全的，并且减少了输注相关不良事件的发生。我们证明，离体慢病毒修饰、雷帕霉素条件化的 CD4+ T 细胞也可以充当下一代细胞递送载体（即“微药剂”），以传播针对多种溶酶体贮积症的纠正酶。我们在体外和体内评估了该治疗平台对法布里病、戈谢病、法伯病和庞贝病的治疗潜力。例如，将表达用于治疗法布里病的α-半乳糖苷酶A的微药剂移植到小鼠体内，它们在肾脏和心脏等关键受影响组织中提供功能酶，从而在单次给药后促进致病底物的清除。