| 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
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987) |
