| Title: | In vitro and in vivo correlation of skin and cellular responses to nucleic acid delivery |
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| Authors: | ID Omerzel, Maša (Author)
ID Žnidar, Katarina (Author)
ID Sales Conniff, A. (Author)
ID Jesenko, Tanja (Author)
ID Markelc, Boštjan (Author)
ID Tur, Jared (Author)
ID Semenova, Nina (Author)
ID Kohena, Kristopher (Author)
ID Kranjc Brezar, Simona (Author)
ID Heller, Loree C. (Author)
ID Čemažar, Maja (Author) |
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| Files: |  URL - Source URL, visit https://www.sciencedirect.com/science/article/pii/S0753332222004772
 PDF - Presentation file, download (7,72 MB)
MD5: BB681153CA2264247A6621319E566BA2
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  OI - Institute of Oncology
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| Abstract: | Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immuno- genicity of skin, we correlated the effects of pDNA electrotransfer to fibroblasts and keratinocytes to mouse skin using reverse transcription real-time PCR (RT-qPCR) and several types of protein quantification. After pDNA electrotransfer, the mRNAs of the putative DNA sensors DEAD (AspGlu-Ala-Asp) box polypeptide 60 (Ddx60), absent in melanoma 2 (Aim2), Z-DNA binding protein 1 (Zbp1), interferon activated gene 202 (Ifi202), and interferon-inducible protein 204 (Ifi204) were upregulated in keratinocytes, while Ddx60, Zbp1 and Ifi204 were upregulated in fibroblasts. Increased levels of the mRNAs and proteins of several cytokines and chemokines were detected and varied based on cell type. Mouse skin experiments in vivo confirmed our in vitro results with increased expression of putative DNA sensor mRNAs and of the mRNAs and proteins of several cytokines and chemokines. |
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| Keywords: | DNA sensors, cytokines, electrotransfer, skin |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 01.06.2022 |
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| Publisher: | Elsevier Masson SAS |
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| Year of publishing: | 2022 |
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| Number of pages: | str. 113088-1-113088-13 |
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| Numbering: | Vol. 150 |
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| PID: | 20.500.12556/DiRROS-15448  |
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| UDC: | 602.6/.7 |
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| ISSN on article: | 0753-3322 |
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| DOI: | 10.1016/j.biopha.2022.113088 |
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| COBISS.SI-ID: | 107308035 |
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| Copyright: | by Authors |
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| Publication date in DiRROS: | 06.09.2022 |
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| Views: | 1048 |
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| Downloads: | 540 |
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| Metadata: |    |
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