Volume 5 Supplement 1

Abstracts from the EAACI Skin Allergy Meeting 2014

Open Access

Effects of interference with GATA-3 expression by target-specific DNAzyme treatment on disease progression in a subacute oxazolone-induced mouse model of atopic dermatitis

  • Rouba Ibrahim1,
  • Ulrich Purath2,
  • Agnieszka Turowska2,
  • Ursula Homburg2,
  • Frank Runkel3,
  • Thomas Schmidts3,
  • Dorota Dobler3,
  • Harald Renz1,
  • Holger Garn1 and
  • Anke Mueller2
Clinical and Translational Allergy20155(Suppl 1):O21

DOI: 10.1186/2045-7022-5-S1-O21

Published: 11 March 2015

Background

DNAzymes represent a particular class of antisense molecules combining the specificity of antisense molecules with an inherent catalytic cleavage activity, which makes them an attractive tool for highly specific interference with target RNA molecules. In general, they are single-stranded DNA molecules with sequence-specific RNA-binding domains flanking a central catalytic domain. We developed and patented a DNAzyme - named hgd40 – that targets the mRNA for GATA-3, the central transcription factor in T helper cell type 2 (Th2) differentiation and activation. For penetration enhancement and DNAzyme protection a specific water/oil/water emulsion for topical dermal application was developed and patented. Targeting GATA-3 might be a key for therapeutic intervention in predominantly Th2-driven diseases like atopic dermatitis.

Method

The therapeutic effects of hgd40 were analyzed in an oxazolone-induced dermatitis model modified to establish elongated skin swelling reactions, thereby enabling the analysis of treatment effects on T cell-mediated pathomechanisms.

Results

Treatment with topically applied hgd40 water/oil/water emulsion significantly and dose-dependently reduced oxazolone-induced skinfold thickness and suppressed infiltration of CD4+ T cells into the skin. Molecular analysis revealed reduced GATA-3 mRNA levels early during disease progression.

Conclusion

In summary, targeting GATA-3 by DNAzyme treatment may represent a new and promising therapeutic agent for the topical treatment of allergic skin diseases.

Authors’ Affiliations

(1)
Philipps University of Marburg, Inst. of Laboratory Medicine and Pathobiochemistry
(2)
sterna biologicals, ZTI
(3)
University of Applied Sciences, IBPT

Copyright

© Ibrahim et al; licensee BioMed Central Ltd. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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