Yaba-like disease virus: an alternative replicating poxvirus vector for cancer gene therapy.
Yaba-like disease virus: an alternative replicating poxvirus vector for cancer gene therapy.
复制标题
亚巴样疾病病毒：用于癌症基因治疗的替代复制痘病毒载体。
DOI：
10.1128/jvi.75.21.10300-10308.2001
复制
发表时间：
2001
影响因子：
5.4
通讯作者：
Bartlett,DL
中科院分区：
文献类型：
--
作者：
Hu,Y;Lee,J;McCart,JA;Xu,H;Moss,B;Alexander,HR;Bartlett,DL
牛痘病毒正被研究作为肿瘤基因治疗的复制载体。然而，由于接种天花疫苗，大多数癌症患者对牛痘病毒产生了免疫反应，这可能限制了牛痘病毒作为载体的使用。雅巴样病（YLD）病毒被研究作为癌症基因治疗的替代，复制痘病毒。我们已经证明YLD病毒不与牛痘病毒抗体交叉反应，并且它在人肿瘤细胞中有效地复制。在牛痘病毒的条件下，YLD病毒可以在CV-1细胞中扩增和纯化到高滴度。YLD病毒RNA聚合酶能够表达由专为正痘病毒设计的合成启动子调控的基因。我们对YLD病毒的TK基因进行了测序，并创建了一个穿梭质粒，使绿色荧光蛋白（GFP）基因能够重组到YLD病毒中。在小鼠卵巢癌模型中，高达38%的肿瘤细胞在腹腔内传递病毒12天后表达GFP转基因。YLD病毒具有作为肿瘤基因治疗载体的良好特性，其潜力有待进一步挖掘。
Vaccinia virus is being investigated as a replicating vector for tumor-directed gene therapy. However, the majority of cancer patients have preformed immunologic reactivity against vaccinia virus, as a result of smallpox vaccination, which may limit its use as a vector. The Yaba-like disease (YLD) virus was investigated here as an alternative, replicating poxvirus for cancer gene therapy. We have demonstrated that the YLD virus does not cross-react with vaccinia virus antibodies, and it replicates efficiently in human tumor cells. YLD virus can be expanded and purified to high titer in CV-1 cells under conditions utilized for vaccinia virus. The YLD virus RNA polymerase was able to express genes regulated by a synthetic promoter designed for use in orthopoxviruses. We sequenced the YLD virus TK gene and created a shuttle plasmid, which allowed the recombination of the green fluorescent protein (GFP) gene into the YLD virus. In a murine model of ovarian cancer, up to 38% of cells in the tumor expressed the GFP transgene 12 days after intraperitoneal virus delivery. YLD virus has favorable characteristics as a vector for cancer gene therapy, and this potential should be explored further.