Von Seggern D J, Kehler J, Endo R I, Nemerow G R
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Gen Virol. 1998 Jun;79 ( Pt 6):1461-8. doi: 10.1099/0022-1317-79-6-1461.
Adenovirus-based gene therapy vectors now in use cannot be targeted to specific cell types in vivo and are immunogenic, properties which limit their clinical utility. Improved vectors lacking the genes for viral structural proteins may overcome these limitations. We have developed cell lines which stably express the adenovirus type 5 (Ad5) fibre protein in its native trimeric form. These cells can complement an Ad5 mutant with a defect in the fibre gene, and are capable of incorporating the Ad5 fibre into particles of a different Ad serotype. As the fibre protein is responsible for the initial binding of virus to cells, packaging cell lines expressing different or modified fibre proteins will be useful in studying the mechanism by which adenovirus infects different cell types.
目前正在使用的基于腺病毒的基因治疗载体在体内不能靶向特定细胞类型,且具有免疫原性,这些特性限制了它们的临床应用。缺乏病毒结构蛋白基因的改进型载体可能会克服这些限制。我们已经开发出稳定表达天然三聚体形式的5型腺病毒(Ad5)纤维蛋白的细胞系。这些细胞可以补充纤维基因有缺陷的Ad5突变体,并能够将Ad5纤维整合到不同腺病毒血清型的颗粒中。由于纤维蛋白负责病毒与细胞的初始结合,表达不同或修饰的纤维蛋白的包装细胞系将有助于研究腺病毒感染不同细胞类型的机制。