Project III - Molecular Characterization of Liver gene transfer and its oncogenic potentialA substantial advantage of AAV for genetic diseases is its ability to confer long-term and high-leveltransgene expression in liver. This project will evaluate several interesting aspects of molecular biology as itrelates to mechanisms of persistence and potential safety considerations. The first specific aim will addressthe potential for recombination between the transduced vector genome and the latent wild-type AAV thatoccurs subsequent to a natural infection. The second specific aim will undertake a systematic evaluation ofthe molecular state and structure of persistent AAV genomes with a focus on the frequency and distributionof integration sites. The final specific aim will undertake experiments to actually quantitate the oncogenicpotential of AAV following the delivery to liver. These studies will be performed in a number of murinemodels including OTCD mice and a model of chronic hepatitis. In addition, the consequence of chronicinflammation on the oncogenic potential of AAV will be studied.Project 3 will rely on Projects 1 and 2 for obtaining tissues from nonhuman primates who have received AAVvectors as part of its goal to undertake molecular characterization. This project will rely on the expertise ofDr. Batshaw in Project 2 to conduct the tumors studies in OTC-deficient mice.Lay description. This project will evaluate the molecular structure of the transferred gene as is resides in theliver cells. Animal studies will be performed to determine if the vector causes tumors.
Showing the most recent 10 out of 26 publications
