Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis
Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis
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DOI：
10.1002/ana.20453
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发表时间：
2005-05-01
影响因子：
11.2
通讯作者：
Cleveland, DW
中科院分区：
文献类型：
--
作者：
Miller, TM;Kaspar, BK;Cleveland, DW
超氧化物歧化酶的突变导致家族性遗传性心脏病的一个子集。肌萎缩侧索硬化症在小鼠体内表达时会引起进行性瘫痪。在肌肉注射后逆行运输到脊髓后，携带编码小干扰RNA的基因的腺相关病毒被证明以超氧化物歧化酶信使RNA为目标进行降解。相应地，脊髓运动神经元中突变的超氧化物歧化酶的减少保持了握力。这一发现为选择性减少任何神经元蛋白提供了原理证据，并支持肌肉内注射一种小型干扰RNA编码病毒作为这种类型的家族性肌萎缩侧索硬化症的可行治疗方法。
Mutations in superoxide dismutase cause a subset of familial. amyotrophic lateral sclerosis and provoke progressive paralysis when expressed in mice. After retrograde transport to the spinal cord following injection into muscles, an adeno-associated virus carrying a gene that encodes a small interfering RNA was shown to target superoxide dismutase messenger RNA for degradation. The corresponding decrease in mutant superoxide dismutase in spinal motor neurons preserved grip strength. This finding provides proof of principle for the selective reduction of any neuronal protein and supports intramuscular injections of a small interfering RNA-encoding virus as a viable therapy for this type of familial amyotrophic lateral sclerosis.