Prolonged survival of heart allografts transduced with AAV-CTLA4Ig

✍ Scribed by Zongyou Chen; Lina Lu; Juan Li; Xiao Xiao; John J. Fung; Shiguang Qian

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 175 KB
• Volume: 23
• Category: Article
• ISSN: 0738-1085
• DOI: 10.1002/micr.10181

✦ Synopsis

Abstract

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 β‐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. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:489–493 2003