Folate immobilized and PEGylated adenovirus for retargeting to tumor cells

The surface of adenovirus (ADV) was modified with folate-poly(ethylene glycol) (FOL-PEG) conjugate to overcome the inherent problems associated with viral gene therapy. The ADV coding the green fluorescent protein (GFP) gene was used to immobilize PEG or FOL-PEG conjugate on the viral surface to comparatively evaluate their extents of retargeting and immune response, as compared to those of naked ADV. The FOL-PEG immobilized ADV exhibited a greatly enhanced level of GFP expression than naked or PEG immobilized ADV for a folate receptor overexpressing cell line (KB cells), but not for a folate receptor deficient cell line (A549 cells), suggesting that the retargeting of ADV could be achieved by immobilizing FOL-PEG conjugate. The ADV immobilized with PEG or FOL-PEG also significantly lowered innate immune response, as judged from the amount of interleukin 6 released from macrophage cells.