Porcine animals lacking any expression of functional alpha 1, 3 galactosyltransferase

• US 7,795,493 B2
• Filed: 08/21/2003
• Issued: 09/14/2010
• Est. Priority Date: 08/21/2002
• Status: Active Grant

• Current Assignee: Revivicor, Inc (United Therapeutics Corporation)
• Original Assignee: Revivicor, Inc (United Therapeutics Corporation)
• Inventors: Ayares, David L., Phelps, Carol J.
• Primary Examiner(s): Falk; Anne-Marie
• Assistant Examiner(s): Sgagias; Magdalene K
• Application Number:
  US10/646,970
• Publication Number:
  US 20040268424A1
• Time in Patent Office: 2,581 Days
• Field of Search: 800/8, 800/17, 800/24, 435/325, 435/1.1
• US Class Current: 800/17
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/108 Swine
• CPC Class Codes: A01K 2267/02 Animal zootechnically ameliorated
• CPC Class Codes: A01K 2267/025 Animal producing cells or organs for transplantation
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 9/2465 acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22)

Abstract

The present invention is a porcine animal, tissue, organ, cells and cell lines, which lack any expression of functional alpha 1,3 galactosyltransferase (alpha1,3GT). These animals, tissues, organs and cells can be used in xenotransplantation and for other medical purposes.

Claims

1. A method for the production of a pig that lacks any expression of functional alpha-1,3 galactosyltransferase (α

-1,3 GT) comprising;

breeding a male pig heterozygous for an inactivation of the alpha-1,3 GT gene with a female pig heterozygous for an inactivation of the α

-1,3 GT gene, wherein one or both pigs are heterozygous due to the presence of a point mutation in an allele of the α

-1,3 GT gene, wherein the point mutation is a T-to-G point mutation at the second base of exon 9 of the α

-1,3 GT gene or a point mutation induced or produced by a genetic modification in the α

-1,3 GT gene.

2. The method of claim 1, wherein the point mutation is a T-to-G point mutation at the second base of exon 9 of the α

-1,3 GT gene.

3. The method of claim 1, wherein a male pig that contains a T-to-G point mutation at the second base of exon 9 of the α

-1,3 GT gene is bred with a female pig that contains a T-to-G point mutation at the second base of exon 9 of the α

-1,3 GT gene.

4. The method of claim 1, wherein at least one of the male or female pigs comprises at least one allele of an α

-1,3 GT gene that is inactivated via a genetic targeting event.

5. The method of claim 1, further comprising breeding together the pigs that lack any expression of functional α

-1,3 GT to produce a herd of pigs that lack any expression of functional α

-1,3 GT.

6. A non-naturally occurring pig produced according to the method of claim 1, 2, 3, 4 or 5.

7. A cell, tissue, or organ obtained from the pig of claim 6.

8. The cell, tissue or organ of claim 7 wherein at least one allele of an α

-1,3 GT gene is inactivated via a genetic targeting event.