METHOD FOR MULTIPLE PORTAL-VEIN INFUSIONS IN MICE - QUANTITATION OF ADENOVIRUS-MEDIATED HEPATIC GENE-TRANSFER

For many preclinical studies, the mouse has been an invaluable model. For hepatic studies, including gene therapy the use of the mouse has b een limited because of the inability to obtain long-term portal vein a ccess. In this study, we have developed a surgical cannula model that allows for repeat portal vein infusion in a noninvasive manner. We hav e used this model to establish that the tissue distribution of recombi nant adenoviral vectors is similar after portal vein or peripheral vei n infusion. The majority of the vector was present in the liver; rangi ng from 14 to 28 copies per hepatocyte. The second most prevalent tiss ues were the spleen and lung with 1/10 less adenoviral DNA. The brain and ovaries had the least DNA, 1/1000 less than the liver. Additional studies were performed to study the effects of secondary adenovirus in fusion through the portal vein cannula. Permanent portal vein access i n a mouse model will be invaluable for a large number of medical studi es, including the development of new technologies for hepatic gene tra nsfer.