Construction of a Helper-dependent Adenoviral Vector and Its application to Mice.
First-generation adenoviral vector with E1 and E3 deleted can effectively deliver foreign genes into target cells and leads to high level of expression of transgenes, but it leads only to transient expression because of the cellular immunity against early and late viral antigens expressed in targeted cells. In order to overcome these difficulties, we have recently developed a helper-dependent recombinant adenovirus vector HAdI-hFVIII in which a large part of the viral genome, including l3, L1, L2, VAI-VAII and pTP regions, was deleted. The novel viral vector DNA can be effectively packaged, amplified in 293 packaging cells co-transfected with an E1-substituted AdI-hFVIII in trans and can be easily separated from helper virus by gradient centrifugation. The hFVIII expression was found in mice after intravenous injection of the new vector. The duration of hFVIII protein in plasma of mice was prolonged compared to that of AdI-hFVIII after injection. It suggests that the novel vector could be less immunogenic in vivo.
Jiang
Zhi-Long
ZL
The Research Center for Human Gene Therapy, Department of Biochemistry and Molecular Biology, Shanghai Second Medical University, Shanghai 200025, China.
Lu
Jian
J
Chen
Shi-Shu
SS