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• W2016090513 abstract "RNA interference (RNAi) mediates sequence-specific gene silencing, which can be harnessed to silencing disease-causing genes for therapy. Particularly suitable diseases are those caused by dominant, gain-of-function type of gene mutations. In these diseases, the mutant gene generates a mutant protein or RNA product, which possesses toxic properties that harm cells. By silencing the mutant gene, the toxicity can be lessened because the amount of the toxic product is lowered in cells. In this report, we tested RNAi therapy in a mouse model for amyotrophic lateral sclerosis (ALS), which causes motor neuron degeneration, paralysis, and death. We used a transgenic model that overexpresses mutant Cu, Zn superoxide dismutase (SOD1G93A), which causes ALS by a gained toxic property. We delivered RNAi using recombinant adenovirus (RAd) and adeno-associated virus serotype 2 (AAV2). We compared the efficiency of RNAi delivery between injecting the viral vectors into muscle and into nerve, and found that nerve injetion is more efficient in delivering RNAi to motor neurons. Based on this data, we conducted therapeutic trials in the mouse model and found that nerve injection of RAd, but not AAV2, at the disease onset had a modest therapeutic efficacy. These results highlight the potential and the challenges in delivering RNAi therapy by gene therapy." @default.
• W2016090513 created "2016-06-24" @default.
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• W2016090513 date "2009-07-01" @default.
• W2016090513 modified "2023-10-17" @default.
• W2016090513 title "Nerve Injection of Viral Vectors Efficiently Transfers Transgenes into Motor Neurons and Delivers RNAi Therapy Against ALS" @default.
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• W2016090513 doi "https://doi.org/10.1089/ars.2009.2618" @default.
• W2016090513 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2842583" @default.
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