腺相关病毒9型-尼曼-皮克病蛋白1（AAV9-NPC1）可显著改善小鼠尼曼-皮克病中的浦肯野细胞死亡和行为异常。
AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse NPC disease.
作者信息
Xie Chang, Gong Xue-Min, Luo Jie, Li Bo-Liang, Song Bao-Liang
机构信息
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan 430072, China.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
出版信息
J Lipid Res. 2017 Mar;58(3):512-518. doi: 10.1194/jlr.M071274. Epub 2017 Jan 4.
Abstract
Niemann-Pick type C (NPC) disease is a fatal inherited neurodegenerative disorder caused by loss-of-function mutations in the or gene. There is no effective way to treat NPC disease. In this study, we used adeno-associated virus (AAV) serotype 9 (AAV9) to deliver a functional gene systemically into mice at postnatal day 4. One single AAV9-NPC1 injection resulted in robust NPC1 expression in various tissues, including brain, heart, and lung. Strikingly, AAV9-mediated NPC1 delivery significantly promoted Purkinje cell survival, restored locomotor activity and coordination, and increased the lifespan of mice. Our work suggests that AAV-based gene therapy is a promising means to treat NPC disease.
摘要
尼曼-匹克C型（NPC）病是一种致命的遗传性神经退行性疾病，由NPC1或NPC2基因的功能丧失突变引起。目前尚无治疗NPC病的有效方法。在本研究中，我们使用9型腺相关病毒（AAV9）在出生后第4天将功能性NPC1基因全身递送至Npc1−/−小鼠体内。单次注射AAV9-NPC1可使包括脑、心脏和肺在内的各种组织中NPC1大量表达。令人惊讶的是，AAV9介导的NPC1递送显著促进了浦肯野细胞的存活，恢复了运动活性和协调性，并延长了Npc1−/−小鼠的寿命。我们的工作表明，基于AAV的基因治疗是治疗NPC病的一种有前景的方法。
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