Adenovirus Mediates Lentiviral Vector Entry for Gene Delivery

Purpose To test the hypothesis that adenovirus may improve gene transfer efficiency of lentiviral vector by mediating viral entry. Methods Adenoviral vector was covalently modified by polylysine and physically conjugated with non-pseudotyped lentiviral vector.The properties of lentivirus-mediated gene expression was investigated,viral entry was observed by confocal microscopy laser scanning using this adenovirus/lentivirus conjugated system.Antibody against adenovirus knob structure was used to see whether it could eliminate this change. Results Lentiviral vector(Lenti -VSVG) carrying β-galactosidase(β-gal) gene was not infectious to HeLa cells due to the lack of viral envelope protein VSV-G.However,the infectivity was recovered in a ratio-dependent manner when Lenti -VSVG was conjugated with adenovirus(AdenoPL) through polylysine molecules.Confocal microscopy studies indicated that Lenti -VSVG uptake by cells was significantly increased by linking to adenovirus vector. Antibody against adenovirus knob structure blocked transgene expression from both adenovirus (green fluorescent protein,GFP) and lentivirus (β-gal). Conclusions Lentiviral vector can transduce cells efficiently through an alternative entry pathway mediated by adenovirus.