Folate immobilized and PEGylated adenovirus for retargeting to tumor cells

tThe 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.