Andenovirus-Mediated Gene Transfer

The injection of a recombinant adenoviral vector into the tail vein of a mouse results in highly preferential infection of the liver and subsequent liver-specific expression of the genes that are inserted into the adenoviral backbone. These characteristics of systemic adenovirus injection, and the fact that adenoviral vectors are relatively easy to generate and amplify to high titers, provide an exquisite and extremely powerful means to investigate the effects of liverspecific expression of a given gene. Moreover, since any transgenic mouse model can be injected with adenoviral vectors, this technology allows rapid analysis of (trans)gene-gene interaction. This chapter focuses on the generation and application of first-generation adenoviral vectors to express genes specifically in the livers of mice. First-generation vectors reach peak transgene expression typically 4–5 days after tail vein injection, and expression can be detected for up to 2 weeks after injection. Thus, the biologic effects of the transgene product should be detectable within this relatively short period of transgene expression. However, it has been demonstrated for many physiologic processes, including, for example, lipoprotein metabolism and blood coagulation, that this period of gene expression is sufficient to determine the effect of overexpression of the protein under investigation.