Liu Ta-Chiang, Thorne Stephen H, Kirn David H
Brain Tumor Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Methods Mol Biol. 2008;433:243-58. doi: 10.1007/978-1-59745-237-3_15.
The use of replication-competent oncolytic viruses has largely advanced cancer gene therapy. Oncolytic virus not only possesses unique mechanisms of action that are distinct from other treatment modalities, its self-perpetuating nature provides an ideal platform for therapeutic transgene insertion. Tumor selectivity can be achieved by deleting viral genes that are critical for growth in normal cells but dispensable in tumor cells, transcriptional control under tumor-specific promoters, fiber modification targeting tumor-specific cellular receptors, or the use of inherent tumor-specific viruses. Transgene products can be amplified along with viral replication, thus maximizing therapeutic effect. Using adenovirus as a template, this chapter describes common assays used for the study of oncolytic viruses, with special emphasis on in vitro and in vivo viral replication determination.
具有复制能力的溶瘤病毒的应用在很大程度上推动了癌症基因治疗的发展。溶瘤病毒不仅具有与其他治疗方式不同的独特作用机制，其自我增殖的特性为治疗性转基因插入提供了理想平台。通过删除对正常细胞生长至关重要但在肿瘤细胞中可有可无的病毒基因、在肿瘤特异性启动子控制下进行转录、修饰靶向肿瘤特异性细胞受体的纤维蛋白或使用固有的肿瘤特异性病毒，可实现肿瘤选择性。转基因产物可随病毒复制而扩增，从而使治疗效果最大化。本章以腺病毒为模板，描述了用于溶瘤病毒研究的常见检测方法，特别着重于体外和体内病毒复制的测定。
