Genetically Edited Animal

Abstract

The present invention relates to a genetically edited animal, especially to a genetically edited pig in which expression or activity of the RELA protein has been modified. Such pigs have at least partial protection against the African Swine Fever Virus. The invention also provides, a cell nucleus, germ cell, stem cell, gamete, blastocyst, embryo, foetus and/or donor cell of a non-human animal comprising a genetic modification which alters the expression or function of RELA protein, methods for editing the genome of animals and methods for screening the efficacy of a pharmaceutical agent in such an animal.

1 . A genetically edited pig comprising a genetic modification to the sequence of the RELA gene which alters the expression or activity of the RELA protein, wherein the modification results in the following changes in the amino acids of the RELA protein: T448A, S485P and S531P. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The pig of  claim 1  in which all cells of the pig contain the genetic modification. 
     
     
         5 - 10 . (canceled) 
     
     
         11 . The pig of  claim 1  in which the modification is bi-allelic. 
     
     
         12 - 18 . (canceled) 
     
     
         19 . The pig of  claim 1  wherein the RELA gene has been edited such that it comprises a sequence which encodes a RELA protein with a sequence as follows: 
       
         
           
                 
               
                   (SEQ ID NO 9) 
                 
                   LLQLQFDADEDLGALLGNNTDPTVFTDLASVDNSEFQQLLNQGVPMPPHT 
                 
                     
                 
                   AEPMLMEYPEAITRLVTGSQRPPDPAPTPLGASGLTNGLLPDGEDFSSIA 
                 
                     
                 
                   DM. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         20 . The pig of  claim 1  wherein at least a portion of the autologous RELA sequence has been replaced with a sequence which encodes the corresponding warthog ( Phacochoerus  sp.) RELA protein sequence. 
     
     
         21 . The pig of  claim 1  in which a portion of the autologous RELA gene has been removed and the following corresponding sequence, or a variant thereof which encodes the same polypeptide, has been inserted: 
       
         
           
                 
               
                   (SEQ ID NO 11) 
                 
                   GTTTGATgCTGATGAGGACCTGGGGGCCCTGCTCGGCAATAACACTGACCC 
                 
                     
                 
                   GACCGTGTTCACGGACCTGGCATCCGTCGACAACTCTGAGTTTCAGCAGCT 
                 
                     
                 
                   GCTGAACCAGGGTGTAcCcATGCCtCCtCACACAGCcGAGCCCATGCTGAT 
                 
                     
                 
                   GGAaTAtCCTGAGGCcATAACcCGCTTGGTcACAGGcTCgCAGAGACCtCC 
                 
                     
                 
                   CtGCTCCtACTCCtCTGGGGGCCTCgGGGCTgACCAAtGGTcGACC 
                 
                     
                 
                   CTCCTCcCcGGGGACGA gGACTTC 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         22 . The pig of  claim 1  which demonstrates one or more of the following phenotypes: an altered NFkappaB signalling capacity; an altered disease resilience or tolerance; an altered immune response; and an altered stress response. 
     
     
         23 . The pig of  claim 1  which demonstrates improved tolerance to one or more of:
 virus infection; 
 pathogen infection, other than viral infection; and 
 general or specific stressors. 
 
     
     
         24 . The pig of  claim 1  which has improved tolerance to ASFV infection. 
     
     
         25 - 45 . (canceled)