Swine defective for transmission of porcine endogenous retrovirus and uses thereof
Miniature swine whose genomes contain sequences characteristic of pig endogenous retrovirus genes but which are non-infectious to humans are disclosed as sources of organs, tissues and cells for introduction into human recipients afflicted with diseases, or at risk of diseases, whose etiology involves the presence of inadequately functioning organs and for which xenotransplantation of such organs, tissues and cells would have a palliative effect. Methods of producing such animals and for screening animals for the desired properties are also disclosed.
1. A process for producing a human-tropic PERV-free swine from parental swine at least one of which is human-tropic PERV-positive, comprising:
(a) mating a male and a female swine of the same species wherein at least one of said swine is positive for a human-tropic PERV-locus whereby said mating produces offspring; and
(b) screening said offspring for the presence of said human-tropic PERV and selecting offspring free of human-tropic PERV,
thereby producing a human-tropic PERV-free swine.
2. A process for producing a human-tropic PERV-free swine from parental swine at least one of which is human-tropic PERV-positive, comprising:
(a) mating a male and a female swine of the same species wherein at least one of said swine is positive for a human-tropic PERV-locus and thereby producing offspring;
(b) mating a male swine produced in (a) with a female swine produced in (a) wherein at least one of said male and female is positive for a human-tropic PERV-locus and wherein if both are positive for an PERV-locus then said male and female are not each positive for the same human-tropic PERV-locus; and
(c) screening said offspring for the presence of said human-tropic PERV and selecting those offspring that are human-tropic PERV-free thereby producing a human-tropic PERV-free swine.
3. The process of claim 2 wherein said human-tropic PERV-free swine is a miniature swine.
4. The process of claim 3 wherein said miniature swine is of the D/D haplotype.
5. The process of claim 2 wherein said human-tropic PERV loci are determined using oligonucleotide probes.
6. The process of claim 2 wherein both male and female swine mated in step (a) are human-tropic PERV-positive and wherein the offspring of (a) that are mated in (b) are each human-tropic PERV-positive swine.
7. The process of claim 2 wherein said human-tropic PERV-free swine is a miniature swine wherein both male and female swine mated in step (a) are human-tropic PERV-positive and wherein the offspring of (a) that are mated in (b) are each human-tropic PERV-positive swine.
8. The process of claim 7 wherein said miniature swine is of the D/D haplotype.
9. The process of claim 6 wherein the swine mated in (a) are each positive for all but one human-tropic PERV-locus, said male and female so mated are each negative for a different PERV-locus, and the male and female of each mated pair of offspring mated in (b) are each, positive, if at all, for a set of human-tropic PERV-loci with no human-tropic PERV loci in common.
10. The process of claim 9 wherein step (a) comprises mating swine carrying a first set of PERVs and swine carrying a second set of PERVs wherein each of said first and second sets of PERVs comprises at least one PERV not present in the other set, to produce offspring and step (b) comprises mating offspring of (a) whereby such mating is between a first swine that carries PERVs present in both of said first and second sets of PERVs but no PERV not present in both of said first and second sets of PERVs and a second swine that carries the PERVs present in said first and second sets of PERVs but not present in both of said first and second sets of PERVs.
11. The process of claim 10 wherein said swine in step (a) carrying said first set of PERVs is a male swine and said swine in step (a) carrying said second set of PERVs is a female swine.
12. The process of claim 10 wherein said second swine in step (b) is a male swine and said first swine in step (b) is a female swine.
13. The process of claim 12 wherein said swine produced by the said process is a miniature swine.
14. The process of claim 13 wherein said miniature swine is of the D/D haplotype.