α(1,3)-galactosyltransferase knockout swine, tissues and organs
AssigneesThe Curators of the University of Missouri, Immerge Biotherapeutics, Inc.
InventorsBilly N. Day, Robert J. Hawley, Randall S. Prather
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Abstract
The invention relates to the genetic manipulation of non-human animals. More particularly, the invention relates to genetic manipulation of non-human animals to be used for xenotransplantation. The invention provides viable gene knockout swine including swine in which the α(1,3)-galactosyltransferase gene has been disrupted, methods for making such swine, and methods of using the tissues and organs of such swine for xenotransplantation.
Claims18
A knockout swine whose genome comprises a disrupted α(1,3)-galactosyltransferase gene, wherein expression of functional α(1,3)-galactosyltransferase in the knockout swine is decreased as compared to a wild-type swine and tissue from the swine exhibits decreased hyperacute rejection as compared to a wild-type swine tissue.
An isolated swine organ comprising cells, the genome of which comprise a disrupted α(1,3)-galactosyltransferase gene, wherein expression of functional α(1,3)-galactosyltransferase in the isolated organ is decreased as compared to a wild-type organ and wherein the organ exhibits decreased hyperacute rejection as compared to a wild-type swine organ.
A method for producing a knockout swine comprising:
- (a) enucleating a swine oocyte;
- (b) fusing the oocyte with a donor swine fibroblast cell the genome of which comprises a disrupted α(1,3)-galactosyltransferase gene;
- (c) activating the oocyte to produce an embryo;
- and
- (d) implanting the embryo into a surrogate swine, wherein the surrogate swine has initiated estrus, but has not yet completed ovulation, for term delivery to produce a knockout swine whose genome comprises a disrupted α(1,3)-galactosyltransferase gene, wherein expression of functional α(1,3)-galactosyltransferase in the knockout swine is decreased as compared to a wild-type swine, and tissue from the swine exhibits decreased hyperacute rejection as compared to a wild-type swine tissue.
Dependencies are inferred from the claim text.