摘要
腺病毒以其具有的诸多优点被广泛应用于肿瘤基因治疗中.但由于腺病毒载体在体内存在感染效率低、免疫原性强等缺点,限制了其在临床中的作用.为了解决这些问题,研究人员制定了一系列改造腺病毒载体的策略.如通过对纤毛蛋白的改造来增强腺病毒载体感染肿瘤细胞的能力;对六邻体蛋白的改造和对病毒衣壳进行聚乙二醇化处理使得腺病毒载体能够逃逸人体的免疫识别.此外,为了增强腺病毒载体对肿瘤细胞的靶向性和杀伤效力,人们也对病毒载体的基因组进行了富有成效的改造.值得注意的是,肿瘤趋向性细胞载体的研究,为腺病毒介导的肿瘤基因治疗系统提供了一种全新的策略.因此,如何能有机地结合多项改造策略,最大限度地提高腺病毒载体在今后临床应用中的高效性、安全性将是未来研究的重点.本文针对最近肿瘤基因治疗中腺病毒载体改造取得的一些进展做一概述和讨论.
Adenovirus has been widely used in cancer gene therapy for its various advantages. However, its disadvantages, such as inefficient in vivo transduction, high immunogenieity and lack of targeting, limit its clinical application. Researchers have developed a variety of strategies to engineer adenoviral vectors solving these problems. It has been reported that the modification of the fiber proteins could enhance adenovirus capacity to infect tumor cells. Alterations in hexon region and PEGylation of viral capsid were both demonstrated to prevent adenovirus vector being recognized by the immune system. Furthermore, many promising progresses have been made in reconstructing the adenovirus vector genome for targeting and killing tumors. Notably, a novel strategy of cellular vectors improved adenovirus-mediated cancer gene therapy systems. This review will summarize and discuss the recent progresses in the modification of adenovirus vectors, and the implications of combined strategies for the improvement of the safety and clinical applications in future cancer treatments.
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2008年第11期1008-1013,共6页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家重点基础研究发展规划项目(973计划,No.2004CB518804)
国家高技术研究发展计划项目(863计划,No.2006AA02Z126)
浙江省科技支撑与攻关计划面上项目(No.2007C33027)资助~~
关键词
腺病毒载体
基因治疗
肿瘤
改造
adenovirus vectors
gene therapy
tumor
modification
