Tissue products derived from animals lacking any expression of functional alpha 1, 3 galactosyltransferase
View Patent ↗The present invention provides tissues derived from animals, which lack any expression of functional alpha 1,3 galactosyltransferase (alpha-1,3-GT). Such tissues can be used in the field of xenotransplantation, such as orthopedic reconstruction and repair, skin repair and internal tissue repair or as medical devices.
1. A tissue product comprising a tissue stripped of viable cells wherein the tissue is derived from a tissue of a porcine animal in which both alleles of the alpha-1,3-galactosyltransferase gene are inactive, wherein at least one allele is rendered inactive through at least one point mutation, and the animal lacks expression of alpha-1,3-galactosyltransferase.
2. The tissue product of claim 1 , wherein the tissue is a hard tissue.
3. The tissue product of claim 1 , wherein the tissue is a soft tissue.
4. The tissue product of claim 2 , wherein the hard tissue is bone or a fragment or derivative thereof.
5. The tissue product of claim 3 , wherein the soft tissue is selected from the group consisting of skin, dermal, submucosal, ligament, tendon and cartilage or a fragment or derivative thereof.
6. The tissue product of claim 1 , wherein the tissue is a combination of hard and soft tissue.
7. The tissue product of claim 6 , wherein the tissue is a bone-tendon-bone graft.
8. The tissue product of claim 1 , wherein at least one allele of the alpha-1,3-GT gene is rendered inactive by a genetic targeting event.
9. The tissue product of claim 8 , wherein the genetic targeting event is homologous recombination.
10. The tissue product of claim 8 or 9 , wherein the genetic targeting event uses a targeting construct directed to exon 9 of the alpha-1,3-GT gene.
11. The tissue product of claim 8 , wherein both alleles of the alpha-1,3-GT gene are rendered inactive through at least one point mutation.
12. The tissue product of claim 8 , wherein the at least one point mutation of the alpha-1,3-GT gene is a substitution, deletion or insertion mutation or a combination thereof.
13. The tissue product of claim 8 , wherein at least one point mutation of the alpha-1,3-GT gene is a T-to-G point mutation at the second base of exon 9.
14. The tissue product of claim 13 , wherein the T-to-G point mutation at the second base of exon 9 in both alleles of the alpha-1,3-GT gene.
15. The tissue product of claim 8 , wherein an allele of the alpha-1,3-GT gene is rendered inactive through at least two point mutations.
16. The tissue product of claim 8 , wherein the tissue stripped of viable cells is produced by enzymatic treatment.
17. The tissue product of claim 8 , wherein the tissue is bone.
18. The tissue product of claim 8 , wherein the tissue stripped of viable cells is produced by chemical treatment.
19. The tissue product of claim 8 , wherein the tissue is selected from the group consisting of tendon, joint, bone and heart valve.
20. The tissue product of claim 9 or 11 , wherein the tissue can be further processed via crosslinking treatments.
21. The tissue product of claim 17 or 19 , wherein the tissue can be further processed via additional chemical treatments.