Both authors contributed equally to this paper.
An RNAi strategy for treatment of amyotrophic lateral sclerosis caused by mutant Cu,Zn superoxide dismutase
Version of Record online: 10 JAN 2005
Journal of Neurochemistry
Volume 92, Issue 2, pages 362–367, January 2005
How to Cite
Xia, X. G., Zhou, H., Zhou, S., Yu, Y., Wu, R. and Xu, Z. (2005), An RNAi strategy for treatment of amyotrophic lateral sclerosis caused by mutant Cu,Zn superoxide dismutase. Journal of Neurochemistry, 92: 362–367. doi: 10.1111/j.1471-4159.2004.02860.x
- Issue online: 10 JAN 2005
- Version of Record online: 10 JAN 2005
- Received July 23, 2004; revised manuscript received September 7, 2004; accepted September 8, 2004.
- Cu,Zn superoxide dismutase;
- neurodegenerative disease;
- RNA interferance;
Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a neurodegenerative disease characterized by motor neuron degeneration, paralysis and death. One cause of this disease is mutations in the Cu,Zn superoxide dismutase (SOD1) gene. As mutant SOD1 acquires a toxic property that kills motor neurons, by reducing the mutant protein the disease progression may be slowed or prevented. While mutant SOD1 is toxic, the wild-type SOD1 is indispensable for motor neuron health. Therefore, the ideal therapeutic strategy would be to inhibit selectively the mutant protein expression. Previously we have demonstrated that RNA interference (RNAi) can selectively inhibit some mutant SOD1 expression. However, more than 100 SOD1 mutants can cause ALS and all mutants cannot be inhibited selectively by RNAi. To overcome this obstacle, we have designed a replacement RNAi strategy. Using this strategy, all mutants and wild-type genes are inhibited by RNAi. The wild-type SOD1 function is then replaced by designed wild-type SOD1 genes that are resistant to the RNAi. Here we demonstrate the concept of this strategy.