Adeno-associated virus-mediated CTLA4Ig gene transfer protects MHC-mismatched renal allografts from chronic rejection.

Journal of the American Society of Nephrology : JASN
Ariela BenigniGiuseppe Remuzzi

Abstract

Short-term results of renal transplantation have improved considerably in the past 20 yr; however, similar improvements in long-term outcome have not been achieved. The primary cause of late graft loss is chronic rejection that might be treated by gene therapeutic approaches. Ideally, one would like to impair locally the contact between transplant antigen and the host immune system without compromising the generalized immune competence of the recipient. This can be achieved by local expression of the therapeutic protein in the site of interest using gene therapy. Here it is shown that chronic allograft rejection can be prevented effectively by local delivery of recombinant adeno-associated virus (AAV) vectors that encode the CTLA4Ig immunosuppressant protein to the donor kidney in a fully MHC-mismatched rat strain combination. AAV CTLA4Ig prevented progressive proteinuria and protected transplant kidneys from renal structural injury. A population of anergic T cells with regulatory activity, which eventually were responsible for the induction of tolerance, were found in recipient lymph nodes and in the graft as long as 120 d after transplantation. These data indicate that AAV-mediated CTLA4Ig gene transfer to donor graft represe...Continue Reading

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Citations

Oct 4, 2006·Gene Therapy·F Yates, G Q Daley
Feb 15, 2008·International Immunology·Marjaneh RazmaraMark L Tykocinski
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Mar 8, 2017·Scientific Reports·Andrea RemuzziGiuseppe Remuzzi
Jul 7, 2018·Journal of the American Society of Nephrology : JASN·Yoichiro IkedaBenjamin D Humphreys
Mar 19, 2011·Current Opinion in Organ Transplantation·Nicolas ChatauretThierry Hauet

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