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Mol Ther. 2015 Feb;23(2):297-309. doi: 10.1038/mt.2014.239. Epub 2014 Dec 15.

Inhibitory/suppressive oligodeoxynucleotide nanocapsules as simple oral delivery devices for preventing atopic dermatitis in mice.

Author information

1
Interdisciplinary Graduate School of Science and Technology, Shinshu University, Kamiina, Japan.
2
Graduate School of Agriculture, Shinshu University, Kamiina, Japan.
3
1] Interdisciplinary Graduate School of Science and Technology, Shinshu University, Kamiina, Japan [2] Research Fellow of the Japan Society for the Promotion of Science (JSPS), Chiyoda-ku, Japan.
4
Department of Internal Medicine and Clinical Immunology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
5
Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, Kamiina, Japan.
6
Frontier Agriscience and Technology Center (FAST), Shinshu University, Kamiina, Japan.
7
Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
8
1] Interdisciplinary Graduate School of Science and Technology, Shinshu University, Kamiina, Japan [2] Graduate School of Agriculture, Shinshu University, Kamiina, Japan [3] Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, Kamiina, Japan.

Abstract

Here, we report a simple and low-cost oral oligodeoxynucleotide (ODN) delivery system targeted to the gut Peyer's patches (PPs). This system requires only Dulbecco's modified eagle's medium, calcium chloride, ODNs, and basic laboratory equipment. ODN nanocapsules (ODNcaps) were directly delivered to the PPs through oral administration and were taken up by macrophages in the PPs, where they induced an immune response. Long-term continuous oral dosing with inhibitory/suppressive ODNcaps (iODNcaps, "iSG3caps" in this study) was evaluated using an atopic dermatitis mouse model to visually monitor disease course. Administration of iSG3caps improved skin lesions and decreased epidermal thickness. Underlying this effect is the ability of iSG3 to bind to and prevent phosphorylation of signal transducer and activator of transcription 6, thereby blocking the interleukin-4 signaling cascade mediated by binding of allergens to type 2 helper T cells. The results of our iSG3cap oral delivery experiments suggest that iSG3 may be useful for treating allergic diseases.

PMID:
25502904
PMCID:
PMC4445625
DOI:
10.1038/mt.2014.239
[Indexed for MEDLINE]
Free PMC Article

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