Stem Cell Related Patent Number US6331658

Genetically engineered mammals for use as organ donors

Cooper, David K. C.; Oklahoma City, OK, USA
Koren, Eugen; Oklahoma City, OK, USA

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.

Application Number: US1995000379040

Date Filed: 01/27/95

Dated Published: 12/18/01

Assignee: Integris Baptist Medical Center, Inc., Oklahoma City, OK, USA
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA