溶瘤单纯疱疹病毒的叶酸-聚乙二醇化修饰及其生物学活性检测  

Biological Evaluation on Oncolytic Herpes Simplex Virus with PEGylated Folate Modification

作　　者：韦炜[1] 郭冬薇[2] 方煜翔[1] 薛京伦[1] 郭圣荣[2] 田聆[1] 

机构地区：[1]复旦大学生命科学学院遗传学研究所暨遗传工程国家重点实验室,上海200433 [2]上海交通大学药学院,上海200240

出　　处：《生物技术通报》2010年第7期201-207,共7页Biotechnology Bulletin

基　　金："863"计划重点项目(2007AA021010)

摘　　要：溶瘤单纯疱疹病毒(oncolytic HSV)是一种重要的具有临床应用前景的病毒,但是该病毒的感染缺乏肿瘤细胞靶向性,因而在相当程度上限制了其进一步的临床应用。首先把特异结合肿瘤细胞表面叶酸受体的叶酸(FA)与聚乙二醇(PEG)进行化学交联,然后用PEG化的叶酸对溶瘤单纯疱疹病毒G207进行共价表面化学修饰,并检测修饰后的病毒FA-PEG-HSV和PEG-HSV的物理和生物学活性。结果显示,FA-PEG-HSV和PEG-HSV的稳定性较未修饰的HSV有所提高,但病毒活力则分别下降为未修饰HSV的22.5%和27.5%,而FA-PEG-HSV对叶酸受体过表达的肿瘤细胞KB的感染效率则比叶酸受体低表达A549细胞提高了300%。以上结果表明,FA-PEG-HSV是一种成功的叶酸受体靶向性溶瘤病毒复合体。Herpes Simplex Virus I is a promising oncolytic virus in clinical application. However, viral tropism, which direct virus infects normal tissues, is one of the major problems hindered the development of HSV-1. To overcome that, poly（ ethylene glycol） （PEG） or folate conjugated PEG （FA-PEG） was immobilized on the surface of HSV-1, and biological properties were evaluated. PEG- lyated HSV-1 has higher zeta potential value than unmodified virus, suggesting that PEGlyation has increased the stability of I-ISV-1 in colloidal dispersions. The viral viability of PEG-HSV and FA-PEG-HSV was 27.5% and 22.5% compared to naked HSV-1. The retargeting specificity of FA-PEG-HSV towards KB cells （folate receptor overexpression） enhanced 300% compared to A549 cells （folate receptor low expression）. The results showed that FA-PEG-HSV was a successful folate receptor-targeted oncolytic virus.

关 键 词：溶瘤单纯疱疹病毒 叶酸 聚乙二醇化 病毒重靶向 基因治疗 

分 类 号：R373[医药卫生—病原生物学]