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AAV9-mediated engineering of autotransplanted kidney of non-human primates

Gene Ther.. 2017-05; 
TomasoniS, TrionfiniP, AzzolliniN, ZentilinL, GiaccaM, AielloS, LongarettiL, CozziE, BaldanN, RemuzziG, Beni
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… immunosuppression in clinical transplantation. Materials and methods. AAV vector construction. The cDNA for LEA29Y was synthesized from Genscript (Piscataway, NJ, USA) after codon optimization in Macaca fascicularis. The cDNA was …

摘要

Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic antirejection therapy. Gene delivery of the immunomodulatory protein cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here we generated adeno-associated virus type 2 (AAV2) and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro. Serotype 9 was chosen for in vivo experiments owing to a lower frequency of preformed antibodies against the A... More

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