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Stem Cell Related Patent Number US6331658
| Title: | Genetically engineered mammals for use as organ donors | | Inventors: | Cooper, David K. C.; Oklahoma City, OK, USA
Koren, Eugen; Oklahoma City, OK, USA | | Summary: | Described herein are methods of producing non-human tissues or organs which are less susceptible to antibody-mediated rejection by human serum. The invention relates to pig organs with decreased immunogenicity due to the modulation of sialyltransferase or of fucosyltransferase expression. Central to the invention is the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the alpha 1->3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not, or do so in a reduced amount. Provided herein are methods by which animals are produced by homologous recombination of the gene encoding alpha 1->3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of alpha 1->3 galactosyl transferase. Alternately, methods are provided by which animals are produced having reduced amounts of alpha 1->3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation. Several embodiments of the invention are provided. Therapeutic applications include the use of such methods as a source of donor organs for transplantation into humans. | | Abstract: | Methods to manipulate animals such as pigs, and the animals and tissues thereby derived, to reduce their immunogenicity following implantation into humans, are described. These methods are based on the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the .alpha. 1.fwdarw.3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not or do so in a reduced amount. In the preferred embodiment, animals are produced by homologous recombination of the gene encoding .alpha. 1.fwdarw.3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of .alpha. 1.fwdarw.3 galactosyl transferase. In alternative embodiments, animals are produced having reduced amounts of .alpha. 1.fwdarw.3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation. | | US Patent Website: | Click Here for Full Text of Patent | | Title Number: | US6331658 | | Application Number: | US1995000379040 | | Date Filed: | 27/01/1995 | | Date Published: | 18/12/2001 | | Assignee: | Integris Baptist Medical Center, Inc., Oklahoma City, OK, USA
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA |
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