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- 清水 かほり
- 大阪大谷大学薬学部生化学講座
書誌事項
- タイトル別名
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- Development and Characterization of a Novel Adenovirus Vector Exhibiting MicroRNA-mediated Suppression of the Leaky Expression of Adenovirus Genes
- マイクロ RNA オ リヨウ シテ ウイルス イデンシ ノ ハツゲン オ ヨクセイ カノウ ナ シンキ アデノウイルス ベクター ノ カイハツ ト キノウ ヒョウカ
この論文をさがす
説明
Replication-incompetent adenovirus (Ad) vectors have gained attention as gene delivery vehicles. Theoretically, no Ad genes should be expressed following transduction; however, Ad genes are expressed from the vector genome, leading to induction of cellular immunity against Ad proteins and Ad protein-induced toxicity. To suppress the leaky expression of Ad genes, a microRNA (miRNA)-regulated gene expression system was utilized. We developed novel Ad vectors by incorporating targeted sequences of miR-122a or miR-142-3p, which exhibit liver- or spleen-specific expression, respectively, in the 3′-untranslated region (UTR) of the E2A, E4, or pIX genes. These Ad vectors easily grew to high titers comparable to those of a conventional Ad vector in conventional human embryonic kidney 293 cells. The leaky expression of these Ad genes in mouse organs was significantly suppressed by 2- to 100-fold in an miRNA-dependent manner, compared with a conventional Ad vector, by the insertion of the miRNA-targeted sequences. Notably, the Ad vector carrying the miR-122a-targeted sequences into the 3′-UTR of the E4 gene (Ad-E4-122aT) expressed 1.5- to 34-fold higher and longer-term transgene expression and more than 20-fold lower levels of all the Ad early and late genes examined in the liver compared with a conventional Ad vector. miR-122a-mediated suppression of E4 gene expression in the liver significantly reduced the hepatotoxicity that an Ad vector causes via both adaptive and non-adaptive immune responses. Ad-E4-122aT would be a promising framework for efficient gene delivery due to its ability to mediate higher and longer-term transgene expression and lower hepatotoxicity than a conventional Ad vector.<br>
収録刊行物
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- 薬学雑誌
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薬学雑誌 135 (12), 1349-1356, 2015-12-01
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001206128411136
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- NII論文ID
- 130005111950
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- NII書誌ID
- AN00284903
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- ISSN
- 13475231
- 00316903
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- NDL書誌ID
- 026971705
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- PubMed
- 26632150
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可