FIG. 7.
Effect of PEGylation of oncolytic adenovirus with 20K PEG on biodistribution, hepatotoxicity, and the ability of the virus to deplete Kupffer cells. (a) Biodistribution of PEGylated virus 24 hr after injection. Nude mice bearing Hep3B tumors were injected intravenously with 5 × 1010 VG of Ad-GL or Ad-GL-PEG20K. At 24 hr tissues were collected and viral genome concentration was determined by qPCR. (b) Effect of PEGylation with 20K PEG on the hepatotoxicity of Ad-GL. Four-week-old female C57BL/6 mice (n = 5 per group) were injected intravenously via the tail vein with 100 μl of PBS, 1011 VG of Ad-GL in PBS, or 1011 VG of PEGylated Ad-GL in PBS. ALT levels in serum were determined on day 3 after injection. (c) Effect of PEGylation with 20K PEG on depletion of Kupffer cells by predosing with replication-defective adenovirus. Six- to 8-week-old female ICR mice (n = 3 or 4 per group) were injected intravenously via the tail vein with 100 μl of PBS, 3 × 1010 VG of replication-deficient Ad-DsRed in PBS, or 3 × 1010 VG of PEGylated replication-deficient Ad-DsRed in PBS. Four hours later, mice were injected intravenously with 3 × 1010 VG of replication-competent Ad-GL. One day later, expression of luciferase in mouse liver was estimated by whole body bioluminescence imaging. Data are shown as means ± SE.