Fender P, Ruigrok R W, Gout E, Buffet S, Chroboczek J
Institut de Biologie Structurale, Grenoble, France.
Nat Biotechnol. 1997 Jan;15(1):52-6. doi: 10.1038/nbt0197-52.
Recombinant adenovirus is one of most efficient delivery vehicles for gene therapy. However, the initial enthusiasm for the use of recombinant adenovirus for gene therapy has been tempered by strong immune responses that develop to the virus and virus-infected cells. Even though recombinant adenoviruses are replication-defective, they introduce into the recipient cell, together with the gene of interest, viral genetes that might lead to fortuitous recombination if the recipient is infected by wild-type adenovirus. We propose the use of a dodecahedron made of adenovirus pentons or penton bases as an alternative vector for human gene therapy. The penton is a complex of two oligomeric proteins, a penton base and fiber, involved in the cell attachment, internalization, and liberation of virus into the cytoplasm. The dodecahedron retains many of the advantages of adenovirus for gene transfer such as efficiency of entry, efficient release of DNA from endosomes, and wide range of cell and tissue targets. Because it consists of only one or two adenovirus proteins instead of the 11 contained in an adenovirus virion and it does not contain the viral genome, it is potentially a safer alternative to recombinant adenovirus.
重组腺病毒是基因治疗中最有效的载体之一。然而，将重组腺病毒用于基因治疗的最初热情因针对病毒和病毒感染细胞产生的强烈免疫反应而有所降温。尽管重组腺病毒复制缺陷，但它们会与目的基因一起将病毒基因导入受体细胞，如果受体被野生型腺病毒感染，这些病毒基因可能会导致偶然重组。我们建议使用由腺病毒五聚体或五聚体基底构成的十二面体作为人类基因治疗的替代载体。五聚体是由两种寡聚蛋白——五聚体基底和纤维组成的复合物，参与病毒与细胞的附着、内化以及病毒释放到细胞质中。十二面体保留了腺病毒在基因转移方面的许多优势，如进入效率、从内体有效释放DNA以及广泛的细胞和组织靶向性。由于它仅由一两种腺病毒蛋白组成，而非腺病毒病毒体中所含的11种蛋白，且不包含病毒基因组，因此它可能是重组腺病毒的一种更安全的替代物。
