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This article is part of the supplement: 6th European Workshop on Immune-Mediated Inflammatory Diseases

Open Access Poster presentation

Synthesis and characterization of non-viral liposomal carriers for the local application of siRNA molecules and anti-miRNAs in the therapeutic treatment of psoriasis

Stefanie Bracke1*, Barbara Geusens1, Peter Dynoodt1, Mireille Van Gele1, Reinhart Speeckaert1, Joost Schalkwijk2, Sandra Tjabringa2 and Jo Lambert1

  • * Corresponding author: Stefanie Bracke

Author Affiliations

1 Dept. of Dermatology, Ghent University Hospital, Ghent, Belgium

2 Dept. of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

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Journal of Translational Medicine 2011, 9(Suppl 2):P13  doi:10.1186/1479-5876-9-S2-P13


The electronic version of this article is the complete one and can be found online at: http://www.translational-medicine.com/content/9/S2/P13


Published:23 November 2011

© 2011 Bracke et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Psoriasis is a common inflammatory skin disease with a multifactorial genetic basis. A dysregulated interplay between keratinocytes and infiltrating immune cells underlies the cutaneous inflammation in psoriasis. Keratinocytes are important producers of antimicrobial peptides such as hBD-2 and LL37 and cytokines such as TNF-alpha, which are essential elements in this process of cell-cell communication [1]. Recently, miRNA-203 was identified as an important contributor to this dysfunctional cross talk [2]. We have previously developed a new lipid-based nanosome (SECosome) that enables the effective delivery of siRNA into human skin [3]. The aim of this project is to knockdown mRNA encoding hBD-2, LL37, TNF-alpha and miRNA-203 by tranfection of keratinocytes with SECosomes for the delivery of siRNAs and anti-miRNAs. Ultimately, we want to create a new therapy for psoriasis by intervening at genetic level by means of a topical therapy.

Materials and Methods

An optimized cytokine mix was used to induce a psoriatic phenotype starting from normal human keratinocytes. Complexes of siRNA or anti-miRNA and SECosomes were made and validated prior to transfection. 24h post-tranfection, qPCR analysis was performed to evaluate mRNA expression levels.

Results

Transfection experiments with the complexes showed a stable knockdown efficiency of more than 80% of hBD-2, LL37, TNF-alpha and miR-203 mRNA.

Conclusion

In this in vitro work we prepared and characterized siRNA and anti-miRNA complexes with SECosomes against hBD-2, LL37, TNF-alpha and miR-203 respectively. These complexes efficiently knock-down the targeted genes with concomitant downregulation of the associated proteins. Hereafter we will test the therapeutic applicability of our complexes in xenografted psoriatic skin by topical application.

References

  1. Nestle FO, Kaplan DH, Barker J: Psoriasis.

    N Engl J Med 2009, 361:496-509. PubMed Abstract | Publisher Full Text OpenURL

  2. Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, Norstedt G, Alenius H, Homey B, Scheynius A, et al.: MicroRNAs: novel regulators involved in the pathogenesis of Psoriasis?

    PLoS One 2007, 2:e610. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  3. Geusens B, Van Gele M, Braat S, De Smedt SC, Stuart M, Prow T, Sanchez W, Roberts M, Sanders NN, J L: Flexible Nanosomes (SECosomes) Enable Efficient siRNA Delivery in Cultured Primary Skin Cells and in the Viable Epidermis of Ex Vivo Human Skin.

    Advanced Functional Materials 2010, (20):4077-4090. OpenURL