Designing a suitable delivery vehicle is very important to obtain the desired results in a gene therapy protocol. Human adenoviruses have attracted considerable interest lately for their potential use as delivery vehicles for gene therapy especially for treating genetic disorders, and cancer. Now it has been fully realized that currently available vectors do express some of the viral genes, and therefore, the cells carrying the desired vector are removed from the circulation resulting in transgene expression for a short duration. This suggests that there is a need to cripple the virus further to obtain transgene expression for an extended period of time. Non-human adenoviruses, such as bovine adenovirus type 3 (BAd3) and porcine adenovirus type 3 (PAd3) that do not replicate in human cells but can infect human cells in culture, could provide an attractive alternative to human adenovirus vectors for gene therapy. The long-term objectives are to develop replication-deficient BAd3 and PAd3 vectors for human gene therapy with a purpose of obtaining expression of the desired gene for a long period of time without significant side effects. Initially these vectors containing a reporter gene will be tested in human cell lines and experimental animals to evaluate the level and duration of transgene expression, the levels of vector's early and late gene expression, the state and duration of the presence of vector DNA, the inflammatory response at the site of inoculation in animals, and the host immune response against the vector. These experiments will form the basis for the future studies initially in human tissues and subsequently in a small human trial using either BAd3 or PAd3 vector for correcting a respiratory, hepatic or cardiovascular disorder or in cancer therapy.
