Inhibition of nuclear delivery of plasmid DNA and transcription by interferonγ: hurdles to be overcome for sustained gene therapy
Inhibition of nuclear delivery of plasmid DNA and transcription by interferonγ: hurdles to be overcome for sustained gene therapy
复制标题
干扰素γ抑制质粒DNA的核递送和转录：持续基因治疗需要克服的障碍
DOI：
10.1038/gt.2011.35
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发表时间：
2011
期刊：
影响因子：
5.1
通讯作者：
Takakura Y.
中科院分区：
文献类型：
--
作者：
Zang L;Nishikawa M;Machida K;AndoM;Takahashi Y;Watanabe Y;Takakura Y.
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.
