Reference - Detail
| RRC ID | 18673 |
|---|---|
| Author | Zang L, Nishikawa M, Machida K, Ando M, Takahashi Y, Watanabe Y, Takakura Y. |
| Title | Inhibition of nuclear delivery of plasmid DNA and transcription by interferon γ: hurdles to be overcome for sustained gene therapy. |
| Journal | 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. |
| Volume | 18(9) |
| Pages | 891-7 |
| Published | 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 |
| Times Cited | 2 |
| WOS Category | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | C2C12(RCB0987) |