論文 - 詳細
| RRC ID | 18673 |
|---|---|
| 著者 | Zang L, Nishikawa M, Machida K, Ando M, Takahashi Y, Watanabe Y, Takakura Y. |
| タイトル | Inhibition of nuclear delivery of plasmid DNA and transcription by interferon γ: hurdles to be overcome for sustained gene therapy. |
| ジャーナル | Gene Ther |
| Abstract |
Sustained expression of murine interferon (IFN)-γ (Muγ) was found to be effective in preventing tumor metastasis and atopic dermatitis in mouse models. However, our preliminary experiments suggested that the time-dependent decrease in the Muγ expression was not compensated for by repeated injections of Muγ-expressing plasmid. To identify the mechanism underlying this observation, a reporter plasmid was hydrodynamically injected into mice and the levels of the plasmid, mRNA and reporter protein were measured in mice receiving a pre- or co-administration of Muγ-expressing plasmid. Co-injection of Muγ-expressing plasmid had no significant effects on transgene expression from the reporter plasmid. In contrast, pre-injection of Muγ-expressing plasmid greatly inhibited the expression of the reporter protein. Moreover, pre-injection of Muγ-expressing plasmid also reduced the amount of the reporter plasmid in the nuclear fraction of mouse liver to < 10%, and that of reporter mRNA to < 1%. The degree of reduction in the expression of reporter protein was comparable with the reduction in mRNA. These results indicate that the difficulty in regaining the expression level of IFN-γ is due to the impaired delivery of plasmid to the nucleus and to the suppression of transcription from the plasmid. |
| 巻・号 | 18(9) |
| ページ | 891-7 |
| 公開日 | 2011-9-1 |
| DOI | 10.1038/gt.2011.35 |
| PII | gt201135 |
| PMID | 21451577 |
| MeSH | Animals Cell Nucleus / genetics* Cells, Cultured Gene Expression Gene Transfer Techniques* Hydrodynamics Injections, Intramuscular Interferon-gamma / blood Interferon-gamma / genetics* Male Mice Mice, Inbred ICR Plasmids RNA, Messenger / metabolism Transgenes |
| IF | 4.128 |
| 引用数 | 2 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |