Using cytosine deaminases to diminish retroelement transfer from pigs to humans

Abstract

Transgenic pigs that express one or more non-porcine cytosine deaminases are described as well as methods of making and using such pigs.

1 . A transgenic pig, the nucleated cells of which comprise a nucleic acid construct, said nucleic acid construct comprising a transcriptional unit comprising a regulatory region operably linked to a nucleic acid sequence encoding a non-porcine cytosine deaminase polypeptide, wherein expression of said non-porcine cytosine deaminase polypeptide in at least some of the cells of the pig results, upon co-culture with human cells, in decreased capability of said cells to transmit porcine endogenous retroviruses to the human cells. 
     
     
         2 . The transgenic pig of  claim 1 , wherein said regulatory region is a constitutive promoter. 
     
     
         3 . The transgenic pig of  claim 1 , wherein said porcine regulatory region is a tissue-specific or an organ-specific promoter. 
     
     
         4 . The transgenic pig of  claim 1 , wherein an insulator element and an inverted repeat of a transposon flank each side of said transcriptional unit. 
     
     
         5 . The transgenic pig of  claim 1 , wherein said non-porcine cytosine deaminase is selected from the group consisting of AID, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3E, APOBEC3F, APOBEC3G, and APOBEC3H. 
     
     
         6 . The transgenic pig of  claim 1 , wherein said non-porcine cytosine deaminase is human APOBEC3F or human ABOBEC3G. 
     
     
         7 . Cells derived from the transgenic pig of  claim 1 . 
     
     
         8 . Tissue isolated from the transgenic pig of  claim 1 . 
     
     
         9 . Progeny of said transgenic pig of  claim 1 .