| タイトル |
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en
A KALA-modified lipid nanoparticle containing CpG-free plasmid DNA as a potential DNA vaccine carrier for antigen presentation and as an immune-stimulative adjuvant
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| 作成者 |
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| アクセス権 |
open access |
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| 主題 |
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| 内容注記 |
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Abstract
en
Technologies that delivery antigen-encoded plasmid DNA (pDNA) to antigen presenting cell and their immune-activation are required for the success of DNA vaccines. Here we report on an artificial nanoparticle that can achieve these; a multifunctional envelope-type nanodevice modified with KALA, a peptide that forms alpha-helical structure at physiological pH (KALA-MEND). KALA modification and the removal of the CpG-motifs from the pDNA synergistically boosted transfection efficacy. In parallel, transfection with the KALA-MEND enhances the production of multiple cytokines and chemokines and co-stimulatory molecules via the Toll-like receptor 9-independent manner. Endosome-fusogenic lipid envelops and a long length of pDNA are essential for this immune stimulation. Furthermore, cytoplasmic dsDNA sensors that are related to the STING/TBK1 pathway and inflammasome are involved in IFN-beta and IL-1 beta production, respectively. Consequently, the robust induction of antigen-specific cytotoxic T-lymphoma activity and the resulting prophylactic and therapeutic anti-tumor effect was observed in mice that had been immunized with bone marrow-derived dendritic cells ex vivo transfected with antigen-encoding pDNA. Collectively, the KALA-MEND possesses dual functions; gene transfection system and immune-stimulative adjuvant, those are both necessary for the successful DNA vaccine.
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| 出版者 |
en
Oxford University Press
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| 日付 |
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| 言語 |
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| 資源タイプ |
journal article |
| 出版タイプ |
VoR |
| 資源識別子 |
HDL
http://hdl.handle.net/2115/59281
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| 関連 |
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isIdenticalTo
DOI
https://doi.org/10.1093/nar/gkv008
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| 収録誌情報 |
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en
Nucleic acids research
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巻43
号3
開始ページ1317
終了ページ1331
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| ファイル |
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| コンテンツ更新日時 |
2023-07-26 |
