新型腺病毒载体的制备及其特性研究

Generation and characterization of fibre modified adenovirus vectors

目的:本研究在普通腺病毒载体(Adv)纤毛头节区插入了具有整合素特异性的RGD肽,制备了一种新型RGD-Adv,以克服Adv基因转导的柯萨奇腺病毒受体依赖性。方法:用体外连接法构建RGD-Adv,并考察其基因转效率、稳定性及体外、体内毒性。结果:RGD-Adv可有效地实现向受试细胞转导基因,其转导能力随病毒量的增加而加强。结论:具有av亲和性的RGD-Adv是一种安全高效的新型腺病毒载体,将在基因治疗及实验研究中发挥重要作用。

Objective： In the present study, We developed and assess an integrin-targeted fiber-mutant Ad vector containing the ArgGly-Asp （RGD） peptide motif on the fiber knob for the transfection of melanoma cell lines. Methods： We constructed RGD-Adv by in vitro ligation method, and investigated the efficiency of gene transdution in melanoma cells, studied its stability, in vitro,and in vivo toxicology. Results： For in vivo and in vitro,gene transfer the RGD-Adv more efficient than the vector containing wild type fiber via an CARindependent cell entry pathway. Conclusion： These results revealed that gene delivery by RGD-Adv was more efficient than that byconventional Adv and suggest that a-integrin-targeted Adv will be of great utility for gene therapy and gene transfer experiments.