Modified Infusion Procedures Affect Recombinant Adeno- Associated Virus Vector Type 2 Transduction in the Liver

Recombinant adeno-associated virus (rAAV) vectors have therapeutic potential for the treatment of several types of liver diseases including hepato-deficiency disorders. Most of the preclinical and clinical applications involve the use of adeno-associated vector serotype 2 (AAV-2). However, when this vector is delivered at high doses into the portal vein or hepatic artery, a relatively small number of hepatocytes are stably transduced. We elected to determine if the route of vector administration and altering the vascular delivery route within the liver influenced the relative level of transduction. First, we delivered an AAV vector expressing the human factor IX gene from a liver-specific promoter into the hepatic artery, portal vein, or general circulation of rats. Transgene expression was equal with hepatic artery and portal vein infusion, which was higher than vector administered via peripheral venous infusion. Next, we determined how localized perfusion or changing the vector dwell time affected AAV t...