Immune tolerant Fabry mouse by liver restricted expression become the inevitable material to study efficacy in enzyme replacement therapy with a modified .-N-acetylgalactosaminidase

先前的研究表明，改良后的人类。- n -乙酰半乳糖胺酶（NAGA）-半乳糖苷酶A （GLA）样底物特异性阻止Fabry模型小鼠globotriaosylceramide （Gb3）的储存。此外，该修饰的NAGA几乎不会引起法布里病患者的寓言反应，作为一种新的安全的酶替代治疗法布里病（Fabry disease）的酶替代治疗（ERT）非常有希望。令人惊讶的是，法布里模型小鼠静脉注射改良的NAGA与致死性过敏反应的高发生率相关。在这里，我们报道了通过利用肝脏促进免疫耐受的能力来抑制寓言反应可以在体内实现。NAGA在肝脏特异性NAGA转基因（NAGA- tg）法布里模型小鼠中稳定表达。因此，免疫耐受的NAGA- tg法布里模型小鼠可能成为研究修饰NAGA在ERT中规避免疫和增强疗效的必然材料。

Previous studies have shown that modified human .-N-acetylgalactosaminidase (NAGA) with human .-galactosidase A (GLA)-like substrate specificity prevents globotriaosylceramide (Gb3) storage in Fabry model mouse. Furthermore, this modified NAGA is hardly expected to cause an allegic reaction in Fabry disease patients, it is highly promising as a new and safe enzyme for enzyme replacement therapy (ERT) for Fabry disease. Surprisingly, a modified NAGA intravenously injected into Fabry model mice was associated with a high rate of fatal anaphylaxis. Here, we reported that suppression of allegic reaction can be achieved in vivo by taking advantage of ability of the liver to promote immune tolerance. Expression of NAGA in the liver was accomplished stably in liver-specific NAGA transgenic (NAGA-Tg) Fabry model mice. Therefore, immune tolerant NAGA-Tg Fabry model mice could become the inevitable materials to study evaded immunity and enhanced efficacy in ERT with a modified NAGA.