文章基本信息

标题：Exon skipping of FcεRIβ eliminates expression of the high-affinity IgE receptor in mast cells with therapeutic potential for allergy
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作者：Glenn Cruse ; Yuzhi Yin ; Tomoki Fukuyama 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：49
页码：14115-14120
DOI：10.1073/pnas.1608520113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceWe identified an innovative use for the technique of antisense oligonucleotide-mediated exon skipping to specifically target and down-regulate IgE receptor expression in mast cells. Exon skipping is typically used as part of personalized medicine, where a mutant exon is skipped after sequencing the patients affected genes. Our approach, however, targets a nonmutated gene and an exon that is critical for surface IgE receptor expression. It does not require a personalized approach with genetic sequencing or multiple iterations of oligonucleotides that would require clinical trials. Furthermore, the diseases to be treated with this technology are ideal for local delivery of the oligonucleotides by aerosols or topical cream formulations. Allergic diseases are driven by activation of mast cells and release of mediators in response to IgE-directed antigens. However, there are no drugs currently available that can specifically down-regulate mast cell function in vivo when chronically administered. Here, we describe an innovative approach for targeting mast cells in vitro and in vivo using antisense oligonucleotide-mediated exon skipping of the {beta}-subunit of the high-affinity IgE receptor (Fc{varepsilon}RI{beta}) to eliminate surface high-affinity IgE receptor (Fc{varepsilon}RI) expression and function, rendering mast cells unresponsive to IgE-mediated activation. As Fc{varepsilon}RI{beta} expression is restricted to mast cells and basophils, this approach would selectively target these cell types. Given the success of exon skipping in clinical trials to treat genetic diseases such as Duchenne muscular dystrophy, we propose that exon skipping of Fc{varepsilon}RI{beta} is a potential approach for mast cell-specific treatment of allergic diseases.
关键词：mast cell ; allergy ; IgE receptor ; oligonucleotides ; dermatitis