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Gal Knockout and Beyond
Author(s) -
Zhong R.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01615.x
Subject(s) - xenotransplantation , antibody , transgene , complement system , antigen , immunology , knockout mouse , gene , transplantation , medicine , biology , genetics
Recently, Galα1‐3Galβ1‐4GlcNAc (Gal) knockout (k/o) pigs have been developed using genetic cloning technologies. This remarkable achievement has generated great enthusiasm in xenotransplantation studies. This review summarizes the current status of nonhuman primate experiments using Gal k/o pig organs. Briefly, when Gal k/o pig organs are transplanted into primates, hyperacute rejection does not occur. Although graft survival has been prolonged up to a few months in some cases, the overall results were not better than those using Gal‐positive pig organs with human complement regulatory protein transgenes. Gal k/o pig kidneys rapidly developed rejection which was associated with increased anti‐non‐Gal antibodies. Although the precise mechanisms of Gal k/o pig organ rejection are not clear, it could result from incomplete deletion of Gal, up‐regulation of new antigen (non‐Gal antigen) and/or production of non‐Gal antibodies. Future work in xenotransplantation should place emphasis on further modification of donors, such as combining human complement regulatory genes with Gal k/o, deleting non‐Gal antigens and adding protective/surviving genes or a gene that inhibits coagulation. Induction of donor‐specific T‐ and B‐cell tolerance and promotion of accommodation are also warranted.