Exon skipping of FceRI[Beta] eliminates expression of the high-affinity IgE receptor in mast cells with therapeutic potential for allergy

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 49; p. 14115
• Main Authors: Cruse, Glenn, Yin, Yuzhi, Fukuyama, Tomoki, Desai, Avanti, Arthur, Greer K, Bäumer, Wolfgang, Beaven, Michael A, Metcalfe, Dean D
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 06.12.2016
• Subjects: Allergies; Antigens; Cells; Genetic disorders; Medical treatment
• ISSN: 0027-8424; 1091-6490

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 β-subunit of the high-affinity IgE receptor (Fc...RIβ) to eliminate surface high-affinity IgE receptor (FceRI) expression and function, rendering mast cells unresponsive to IgE-mediated activation. As Fc...RIβ 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 FceRIβ is a potential approach for mast cell-specific treatment of allergic diseases. (ProQuest: ... denotes formulae/symbols omitted.)