Prolonged survival of heart allografts transduced with AAV-CTLA4Ig

Organ grafts transduced with gene-encoding immunosuppressive molecules are a less toxic approach to preventing graft rejection. Adenovirus vectors have been widely tested with unsatisfactory results, while adeno-associated virus (AAV) is smaller and elicits a low host humoral response. We constructed an AAV vector containing the mouse CTLA4Ig gene. B10 (H2(b)) cardiac grafts were transduced with AAV-CTLA4Ig by coronary infusion. AAV-LacZ vectors were used as reporters and controls, and the expression of beta-gal was determined by X-gal staining. Thirty percent to 40% of myocytes displayed strongly positive X-gal staining after infusion with AAV-LacZ. Additional infusion with vascular dilator reagents did not improve the transduction rate. Survival of B10 heart allografts transduced with AAV-CTLA4-Ig was significantly prolonged in C3H (H2(k)) recipients. These data demonstrate that AAV vectors can efficiently be transduced into the mouse myocardium by coronary infusion. Graft transduction with AAV-CTLA4Ig may be a novel approach to preventing allograft rejection.