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Synthesis and characterization of non-viral liposomal carriers for the local application of siRNA molecules and anti-miRNAs in the therapeutic treatment of psoriasis
Journal of Translational Medicine volume 9, Article number: P13 (2011)
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 . Recently, miRNA-203 was identified as an important contributor to this dysfunctional cross talk . We have previously developed a new lipid-based nanosome (SECosome) that enables the effective delivery of siRNA into human skin . 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.
Transfection experiments with the complexes showed a stable knockdown efficiency of more than 80% of hBD-2, LL37, TNF-alpha and miR-203 mRNA.
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.
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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, 4077-4090. 20
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Bracke, S., Geusens, B., Dynoodt, P. et al. Synthesis and characterization of non-viral liposomal carriers for the local application of siRNA molecules and anti-miRNAs in the therapeutic treatment of psoriasis. J Transl Med 9 (Suppl 2), P13 (2011). https://doi.org/10.1186/1479-5876-9-S2-P13
- Skin Disease
- Antimicrobial Peptide
- Topical Therapy
- Psoriatic Skin