Fiber-knob嵌合型溶瘤腺病毒对胶质瘤细胞的体外感染和杀伤活性分析  

Analysis of in vitro Infection and Killing Activity of Fiber-knob Chimeric Oncolytic Adenovirus on Glioma Cells

作　　者：刘文茉 王立正 于彬[1] 于湘晖[1] LIU Wenmo;WANG Lizheng;YU Bin;YU Xianghui(School of Life Sciences,Jilin University,Changchun 130012,China)

机构地区：[1]吉林大学生命科学学院,长春130012

出　　处：《吉林大学学报(理学版)》2025年第1期201-206,共6页Journal of Jilin University:Science Edition

基　　金：国家自然科学基金面上项目(批准号:32071466).

摘　　要：针对恶性胶质瘤是颅内最常见的恶性肿瘤,患者的平均生存时间较短,传统治疗方法难以实现根治,而新兴的溶瘤病毒疗法存在扩散能力有限,治疗效果不理想等问题,通过基因工程技术对人5型腺病毒(Ad5)衣壳蛋白进行修饰,构建一种纤维蛋白头节区(knob)嵌合替换型溶瘤腺病毒,以提升其对胶质瘤细胞的感染和靶向能力.利用来自B亚群Ad37的knob替换Ad5的knob,证实其可利用唾液酸为受体,从而增强对胶质瘤等CAR(coxsackievirus and adenovirus receptor)低表达肿瘤细胞的感染和杀伤能力,并在体外模型中提升对血脑屏障的穿透效率,为恶性胶质瘤的治疗提供新的解决方案.Based on the fact that glioblastoma multiforme is the most common malignant tumor in the brain,an average survival time of patients is relatively short,and traditional treatment methods are difficult to achieve cure.However,emerging oncolytic virotherapy has limited dissemination capability and suboptimal treatment effects.By using genetic engineering technology to modify the capsid protein of human adenovirus type 5(Ad5),we constructed a chimeric oncolytic adenovirus with a fiber knob replacement to enhance its ability to infect and target glioma cells.By replacing the knob of Ad5 with the knob of Ad37 from subgroup B Ad37,it was confirmed that it could utilize sialic acid as a receptor,thereby improving its ability to infect and kill tumor cells with low expression of CAR(coxsackievirus and adenovirus receptor)such as glioma,and improving its penetration efficiency through the blood-brain barrier in in vitro models,providing a new solution for the treatment of glioblastoma multiforme.

关 键 词：恶性胶质瘤 溶瘤腺病毒 基因工程 

分 类 号：Q789[生物学—分子生物学]