Dynamic distribution and expression in vivo of the human interferon gamma gene delivered by adenoviral vector.----中国科学院微生物研究所

科研成果

论文题目:	Dynamic distribution and expression in vivo of the human interferon gamma gene delivered by adenoviral vector.
作者:	Jiangxue Wu, Xia Xiao, Hongyun Jia, Jiemin Chen, Yinghui Zhu, Peng Zhao,Huanxin Lin,Wenlin Huang*
联系作者:	黄文林
刊物名称:	BMC Cancer
期:	55
卷:	9
页:
年份:	2010
影响因子:	2.736
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摘要:	Background: We previously found that r-hu-IFN gamma exerts a potent anti-tumor effect on human nasopharyngeal carcinoma xenografts in vivo. Considering the fact that the clinical use of recombinant IFN gamma is limited by its short half-life and systemic side effects, we developed a recombinant adenovirus, Ad-IFN gamma. Methods: Dynamic distribution of the adenovirus vector and expression of IFN gamma were evaluated by Q-PCR and ELISA after intratumoral administration of Ad-IFN gamma into CNE- 2 xenografts. Results: Ad-IFN gamma DNA was mainly enriched in tumors where the Ad-IFN gamma DNA was injected (P < 0.05, compared to blood or parenchymal organs), as well as in livers (P < 0.05). Concentrations of Ad-IFN gamma DNA in other organs and blood were very low. Intratumoral Ad-IFN gamma DNA decreased sharply at high concentrations (9 x 10(5) copies/mu g tissue DNA), and slowly at lower concentrations (1.7-2.9 x 10(5) copies/mu g tissue DNA). IFN gamma was detected in the tumors and parenchymal organs. The concentration of IFN gamma was highest in the tumor (P < 0.05), followed by the liver and kidney (P < 0.05). High-level intratumoral expression of IFN gamma was maintained for at least 7 days, rapidly peaking on day 3 after injection of Ad-IFN gamma DNA. Conclusion: An IFN gamma gene delivered by an adenoviral vector achieved high and consistent intratumoral expression. Disseminated Ad-IFN gamma DNA and the transgene product were mainly enriched in the liver.