Permanent Lowered HLA Class I Expression using Lentivirus Vectors with siRNA Constructs

HLA matching is important and necessary for renal and bone marrow transplants (Curr Opin Organ Transpl 2004 9:1-7, NEJM 1990.323:1818-1822). Zero-mismatched renal transplants are associated with fewer rejection episodes and longer graft survival, and require less immunosuppression. In adult bone marrow transplantation, it is necessary to have no more than one allele mismatch to obtain maximum engraftment and minimize graft vs host disease. siRNA is a ubiquitous regulatory system which selectively inhibits gene expression; accordingly, we investigated whether siRNA mediated knockdown of Class I HLA would enable allogeneic cells to evade immune recognition.

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