利用人類多瘤性病毒，JC病毒，類病毒殼體作為基因傳輸載體在裸鼠模式下抑制人類肺腺癌生長

Gene transfer by using the human JC virus-like particle to inhibit human lung adenocarcinoma growth in a nude mouse model

彭春怡(Chun-Yi Peng)

指導教授 ： 王梅林

中山醫學大學/醫學院/微生物免疫研究所/碩士(2013年)

摘要

JC病毒屬於人類多瘤性病毒科，會感染免疫缺陷病人的腦部寡突膠細胞，造成進行性多病灶腦白質症。JC病毒的主要結構蛋白VP1在大腸桿菌的蛋白表達系統中會自行組裝成類病毒殼體，並可包裹外來的DNA，因此嘗試將JC病毒的類病毒殼體當作基因輸送的載體，遞送外來基因到人類細胞。在本論文中，以大腸桿菌製造包裹自殺基因的類病毒殼體，再以此類病毒殼體感染人類肺腺癌細胞。在體外實驗中，攜帶自殺基因的類病毒殼體再配合Ganciclovir作用可以毒殺人類肺腺癌細胞。在裸鼠模式中，與控制組相比較下，腫瘤成長的幅度比較小。因此，JC病毒的類病毒殼體有可能發展成為治療人類肺腺癌的基因傳遞載體。

關鍵字

多瘤性病毒 ； 基因治療 ； 人類肺腺癌

並列摘要

JC virus (JCV), a human polyomavirus, belongs to the polyomaviridae. JCV may infect oligodendrocytes of immune deficiency patient and cause progressive multifocal leukoencephalopathy (PML). We generated JCV virus-like particles (VLPs) when the major capsid protein VP1 was expressed in E. coli. The recombinant VLPs were demonstrated to be able to package and deliver exogenous DNA into mammalian cell. These findings indicate that the recombinant JCV VLP potentially could be used as a human gene transfer vector for gene therapy. In this study, a suicide gene, the herpes simplex virus thymidine kinase gene (tk), was encapsidated into VLP in E.coli protein expression system. In vitro study shown that treated cells with tk-VLP can inhibit human lung adenocarcinoma cell growth when added ganciclovir (GCV). The tk-VLP was used to specifically target human lung adenocarcinoma cells in a nude mouse model. Intraperitoneal administration of GCV in the tk-VLP-treated mice inhibited tumor growth when compared with control group. These findings suggest that it will be possible to develop the JCV VLP as a gene delivery vector for human lung adenocarcinoma therapy in the future.

並列關鍵字

polyomavirus ； gene therapy ； human adenocarcinoma

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