Pre-clinical efficacy and dosing of an AAV8 vector expressing human methylmalonyl-CoA mutase in a murine model of methylmalonic acidemia (MMA)
Pre-clinical efficacy and dosing of an AAV8 vector expressing human methylmalonyl-CoA mutase in a murine model of methylmalonic acidemia (MMA)
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DOI：
10.1016/j.ymgme.2012.09.019
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发表时间：
2012-11-01
影响因子：
3.8
通讯作者：
Venditti, Charles P.
中科院分区：
文献类型：
--
作者：
Chandler, Randy J.;Venditti, Charles P.
我们证明，使用AAV血清型8载体递送的人甲基丙二酰辅酶a突变酶（MUT）可以挽救MMA小鼠显示的致死表型，并提供长期的表型校正。除了确定有效剂量的下限外，我们的研究还表明，线粒体加工的物种障碍和对MUT的明显免疫反应都不会限制小鼠模型作为测试人类MMA基因治疗载体疗效的实验平台。Elsevier Inc.出版。
We demonstrate that human methylmalonyl-CoA mutase (MUT), delivered using an AAV serotype 8 vector, rescues the lethal phenotype displayed by mice with MMA and provides long-term phenotypic correction. In addition to defining a lower limit of effective dosing, our studies establish that neither a species barrier to mitochondrial processing nor an apparent immune response to MUT limits the murine model as an experimental platform to test the efficacy of human gene therapy vectors for MMA. Published by Elsevier Inc.