期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 131, 期 10, 页码 2079-2086出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2011.169
关键词
-
类别
资金
- Dystrophic Epidermolysis Bullosa Research Association UK
- Medical Research Council [G0801742, G0802780] Funding Source: researchfish
- MRC [G0801742, G0802780] Funding Source: UKRI
Epidermolysis bullosa simplex (EBS) is an incurable, inherited skin-blistering disorder predominantly caused by dominant-negative mutations in the genes encoding keratins K5 or K14. RNA interference, particularly in the form of small interfering RNA (siRNA), offers a potential therapy route for EBS and related keratin disorders by selectively silencing the mutant allele. Here, using a systemic screening system based on a luciferase reporter gene assay, we have developed mutant-specific siRNAs for two independent EBS-causing missense mutations in the K5 gene (p.Ser181Pro and p.Asn193Lys). The specificity of the allele-specific inhibitors identified in the screen was subsequently confirmed at the protein level, where the lead inhibitors were shown to strongly knock down the expression of mutant proteins with negligible effect on wild-type K5 expression. In a cell-based model system, the lead inhibitors were able to significantly reverse the cytoskeletal aggregation phenotype. Overall, this approach shows promise for the treatment of EBS and paves the way for future clinical trials.
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