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Targeted silencing of DEFB4 in a bioengineered skin‐humanized mouse model for psoriasis: development of siRNA SECosome‐based novel therapies |
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| Authors: | Sara Guerrero‐Aspizua Eline Desmet Nuria Illera Manuel Navarro Jo Lambert Marcela Del Rio |
| Affiliation: | 1. Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, , Valencia, Spain;2. Department of Bioengineering, Carlos III University (UC3M), , Madrid, Spain;3. Department of Dermatology, Ghent University Hospital, , Ghent, Belgium;4. Regenerative Medicine Unit, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), , Madrid, Spain;5. Molecular Oncology Unit, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), , Madrid, Spain |
| Abstract: | Psoriasis is a complex inflammatory skin disease that presents a wide variety of clinical manifestations. Human β defensin‐2 (hBD‐2) is highly up‐regulated in psoriatic lesions and has been defined as a biomarker for disease activity. We explored the potential benefits of targeting hBD‐2 by topical application of DEFB4‐siRNA‐containing SECosomes in a bioengineered skin‐humanized mouse model for psoriasis. A significant improvement in the psoriatic phenotype was observed by histological examination, with a normalization of the skin architecture and a reduction in the number and size of blood vessels in the dermal compartment. Treatment leads to the recovery of transglutaminase activity, filaggrin expression and stratum corneum appearance to the levels similar to those found in normal regenerated human skin. The availability of a reliable skin‐humanized mouse model for psoriasis in conjunction with the use of the SECosome technology may provide a valuable preclinical tool for identifying potential therapeutic targets for this disease. |
| Keywords: | hBD‐2 psoriasis SECosomes siRNA skin‐humanized mouse model |