A DNA Microarray-based Analysis of the Host Response to a Nonviral Gene Carrier: A Strategy for Improving the Immune Response

Hatakeyama, Hiroto; Ito, Erika; Yamamoto, Momoko et al.

Molecular Therapy, 2011, 19(8), 1487-1498

Permalink : https://hdl.handle.net/2115/48250

このアイテムのアクセス数:1,248件（2026-02-09 02:51 集計）

閲覧可能ファイル 

ファイル フォーマット サイズ 閲覧回数 説明
Mol Ther Hatakeyama. Revised Manuscript pdf 236 KB 941
Mol Ther Hatakeyama. Revised Supplementary Materials and Methods pdf 62.2 KB 638 Supplementary Materials and Methods

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権
open access
URI
https://hdl.handle.net/2115/48250
タイトル
A DNA Microarray-based Analysis of the Host Response to a Nonviral Gene Carrier: A Strategy for Improving the Immune Response
著者
Hatakeyama, Hiroto ; Ito, Erika ; Yamamoto, Momoko ; Akita, Hidetaka ; Hayashi, Yasuhiro ; Kajimoto, Kazuaki ; Kaji, Noritada ; Baba, Yoshinobu ; Harashima, Hideyoshi
著者名
Hatakeyama, Hiroto
著者名
Ito, Erika
著者名
Yamamoto, Momoko
著者名
Akita, Hidetaka
著者名
Hayashi, Yasuhiro
著者名
Kajimoto, Kazuaki
著者名
Kaji, Noritada
著者名
Baba, Yoshinobu
著者名
Harashima, Hideyoshi
言語
英語
発行日
2011-08
出版者
Ｎａｔｕｒｅ　Ｐｕｂｌｉｓｈｉｎｇ
収録物名
Molecular Therapy
巻(号)
19(8)
ページ
1487-1498
抄録
The purpose of this study was to investigate the host response to systemically administered lipid nanoparticles (NPs) encapsulating pDNA in the spleen using a DNA microarray. As a model for NPs, we used a Multifunctional envelope-type nano device (MEND). Microarray analysis revealed that 1581 of the differentially expressed genes could be identified by PEG-unmodified NP using a 3-fold change relative to the control. As the result of PEGylation, the NP treatment resulted in the reduction in the expression of most of the genes. However, the expression of type I interferon (IFN) was specifically increased by PEGylation. Based on the microarray and a pathway analysis, we hypothesize that PEGylation inhibited the endosomal escape of NP, and extended the interaction of TLR9 with CpG-DNA accompanied by the production of type I IFN. This hypothesis was tested by introducing a pH-sensitive fusogenic peptide, GALA, which enhances the endosomal escape of PEGylated NP. As expected, type I IFN was reduced and IL-6 remained at the baseline. These findings indicate that a carrier design based on microarray analysis and the manipulation of intracellular trafficking constitutes a rational strategy for reducing the host immune response to NPs.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
PISSN
1525-0016
EISSN
1525-0024
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1038/mt.2011.24