期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 4, 期 -, 页码 -出版社
CELL PRESS
DOI: 10.1038/mtna.2015.14
关键词
expression control; Parkinson's disease(PD); PD fibroblast; PD-model fly; RNAi; siRNA; alpha-synuclein
资金
- Ministry of Health, Labour and Welfare of Japan
- Japan Society for the Promotion of Science [25871169, 24390226]
- Grants-in-Aid for Scientific Research [25871169, 24390226, 26670446, 25670428] Funding Source: KAKEN
The alpha-synuclein (SNCA) gene is a responsible gene for Parkinson's disease (PD); and not only nucleotide variations but also overexpression of SNCA appears to be involved in the pathogenesis of PD. A specific inhibition against mutant SNCA genes carrying nucleotide variations may be feasible by a specific silencing such as an allele-specific RNA interference (RNAi); however, there is no method for restoring the SNCA overexpression to a normal level. Here, we show that an atypical RNAi using small interfering RNAs (siRNAs) that confer a moderate level of gene silencing is capable of controlling overexpressed SNCA genes to return to a normal level; named expression-control RNAi (ExCont-RNAi). ExCont-RNAi exhibited little or no significant off-target effects in its treated PD patient's fibroblasts that carry SNCA triplication. To further assess the therapeutic effect of ExCont-RNAi, PD-model flies that carried the human SNCA gene underwent an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant improvement in their motor function. Our current findings suggested that ExCont-RNAi might be capable of becoming a novel therapeutic procedure for PD with the SNCA overexpression, and that siRNAs conferring a moderate level of gene silencing to target genes, which have been abandoned as useless siRNAs so far, might be available for controlling abnormally expressed disease-causing genes without producing adverse effects.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据