Adenoviral-mediated gene delivery to liver isografts: improved model of ex vivo gene transfer.

PREVIOUS studies using adenoviral vectors in experimental liver transplant settings have demonstrated in vivo infectivity by perfusing grafts with viral vectors. 1•2 However. these techniques required high viral titers (1 to 5 X 1010 plaque-forming units [pfu)) to induce effective viral infection. In this study, we developed an improved gene delivery method that allows near maximal infectivity of adenoviral vector to liver grafts by trapping vector perfusate within the graft for the duration of the cold preservation period. Using this technique. we successfully delivered an adenovirus encoding the human inducible nitric oxide synthase (iNOS) gene to cold-preserved liver grafts. Nitric oxide (NO) has been shown to have protective properties.3 due to its vasoprotective, antiinflammatory and antiapoptotic effects and its activity as a free radical scavenger. We therefore hypothesized that delivery of the iNOS gene to liver grafts will decrease ischemic damage in the early posttransplant period.