Assessment of hepatotoxicity of wild-type Ad5 modified with microRNA binding sites.

<p>(A) Measurement of serum ALT (black bars) and AST (grey bars) 72 h following intravenous administration of 5×10¹⁰ viral particles of wild-type Ad5 and Ad5-mir122. Analysis was performed as described in the <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000440#s4" target="_blank">Methods</a> section. (B) Adenovirus genomes in murine liver were measured by real time PCR 72 h following intravenous administration of 5×10¹⁰ viral particles of wild-type Ad5 WT and Ad5-mir122, as described in the <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000440#s4" target="_blank">Methods</a> section. (C) Assessment of liver histology. The left liver lobe from each mouse was immersed in 10% buffered formalin overnight at room temperature, embedded in wax and sectioned using a vibratome. Sections were stained with haematoxylin and eosin and analysed by light microscopy at ×40 magnification. Mice were treated with PBS, non-replicating E1, E3-deleted Ad5 expressing GFP (Ad5-GFP), wild-type Ad5, or wild-type Ad5 modified to contain 4 mir-122 binding sites, as indicated. (*** P<0.0005).