Inhibition of xenoreactive natural antibody production by retroviral gene therapy
JL Bracy, DH Sachs, J Iacomini - Science, 1998 - science.org
JL Bracy, DH Sachs, J Iacomini
Science, 1998•science.orgThe major barrier to transplantation across discordant species, such as from pig to human, is
rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate
epitope Galα1-3Galβ1-4GlcNAc-R (αGal) on donor tissues. This epitope is synthesized by
the enzyme glucosyltransferase uridine 5′-diphosphate galactose: β-d-galactosyl-1, 4-N-
acetyl-d-glucosaminide α (1-3) galactosyltransferase (EC 2.4. 1.151), or simply αGT. When a
functional αGT gene was introduced by retroviral gene transfer into bone marrow cells, αGal …
rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate
epitope Galα1-3Galβ1-4GlcNAc-R (αGal) on donor tissues. This epitope is synthesized by
the enzyme glucosyltransferase uridine 5′-diphosphate galactose: β-d-galactosyl-1, 4-N-
acetyl-d-glucosaminide α (1-3) galactosyltransferase (EC 2.4. 1.151), or simply αGT. When a
functional αGT gene was introduced by retroviral gene transfer into bone marrow cells, αGal …
The major barrier to transplantation across discordant species, such as from pig to human, is rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate epitope Galα1-3Galβ1-4GlcNAc-R (αGal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5′-diphosphate galactose:β-d-galactosyl-1,4-N-acetyl-d-glucosaminide α(1-3)galactosyltransferase (E.C. 2.4.1.151), or simply αGT. When a functional αGT gene was introduced by retroviral gene transfer into bone marrow cells, αGal XNA production in a murine model ceased. Thus, genetic engineering of bone marrow may overcome humoral rejection of discordant xenografts and may be useful for inducing B cell tolerance.
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