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.
Chen
Zongyou
Z
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Lu
Lina
L
Li
Juan
J
Xiao
Xiao
X
Fung
John J
JJ
Qian
Shiguang
S
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D060908:CTLA-4 Antigen; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors / Q000494:pharmacology*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000235:genetics; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014161:Transduction, Genetic / Q000379:methods
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins