Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.
Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.
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DOI：
10.1038/s41467-022-30847-x
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发表时间：
2022-06-03
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
遗传性糖基磷脂酰肌醇（GPI）缺乏症（IGD）是由GPI生物合成基因的突变引起的。其全身性，尤其是神经系统症状的机制尚未阐明，根本的治疗方法也尚未建立。在此，我们报道了由PIGO突变导致的IGD小鼠模型的建立以及有效基因治疗的研发。由于IGD的临床表现是全身性且持续终身的，我们用腺相关病毒对小鼠进行了治疗，以实现同源不依赖的基因敲入以及Pigo cDNA的染色体外表达。神经元表型和生长缺陷得到了显著改善，为治愈IGD开辟了新途径。
遗传性GPI缺乏症（IGD）是由PIGO突变引起的。在此，作者构建了IGD小鼠模型，并表明腺相关病毒介导的基因治疗，用于Pigo cDNA的基因敲入以及染色体外表达，改善了小鼠的病理状况。
Inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD caused by PIGO mutations as well as development of effective gene therapy. As the clinical manifestations of IGD are systemic and lifelong lasting, we treated the mice with adeno-associated virus for homology-independent knock-in as well as extra-chromosomal expression of Pigo cDNA. Significant amelioration of neuronal phenotypes and growth defect was achieved, opening a new avenue for curing IGDs. Inherited GPI deficiency (IGD) is caused by PIGO mutations. Here, the authors generate a mouse model of IGD and show that AAV-mediate gene therapy, for knock-in as well as extra-chromosomal expression of Pigo cDNA, ameliorates pathology in the mice.
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