Humanized Variable Lymphocyte Receptors (VLR) and Compositions and Uses Related Thereto

Abstract

This disclosure relates to variable lymphocyte receptors (VLRs) modifications such as humanized sequences and polypeptides comprising such sequences that specifically bind a target molecule and uses related thereto. In certain embodiments, the disclosure relates to recombinant polypeptide VLRs disclosed herein and variants thereof. In certain embodiments, this disclosure relates to treating or preventing a disease or condition comprising administering an effective amount of a recombinant polypeptide or variant disclosed herein to a subject in need thereof.

1 . A recombinant vector comprising a nucleic acid encoding a polypeptide comprising an amino acid sequence XLXLXXNKLQTIAKGTFSPLRAIQXMXLXX (SEQ ID NO: 38) wherein X at each position is individually and independently any amino acid provided that the polypeptide does not contain at least one of the following wild-type Slit2-D2 sequences selected from (SEQ ID NO: 16) LLSLYD, and (SEQ ID NO: 17) TMHLAQ. 
     
     
         2 . The recombinant vector of  claim 1 , wherein the polypeptide comprises an amino acid sequence 
       
         
           
                 
               
                   (SEQ ID NO: 71) 
                 
                 
                 
               
                     
                   DLHNLNYLDLNNNKLQTIAKGTFSPLRAIQHMWLYQNPFICDC. 
                 
             
                
               
            
             
                
               
            
           
         
       
     
     
         3 . The recombinant vector of  claim 1 , wherein the polypeptide comprises an amino acid sequence 
       
         
           
                 
               
                   (SEQ ID NO: 24) 
                 
                 
               
                   CPAACTCSNNIVDCRGKGLTEIPTNLPETITEIRLEQNTIKVIPPGAFSP 
                 
                     
                 
                   YKKLRRIDLSNNQISELAPDAFQGLRSLNSLDLGGNKITELPKSLFEGLF 
                 
                     
                 
                   SLQLLLLNANKINXLRVDAFQDLHNLNLLSLDDNKLQTIAKGTFSPLRAI 
                 
                     
                 
                   QTMHLAQNPFICDCHLKWLADYLSIAMRWDGKAVNDPDSARCTSPRRLAN 
                 
                     
                 
                   KRIGQIKSKKFRC. 
                 
             
                
               
            
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . The recombinant vector of  claim 1 , wherein the polypeptide comprises an amino acid sequence 
       
         
           
                 
               
                   (SEQ ID NO: 1) 
                 
                 
               
                   CPAACTCSNNTVDCRSKGLTEIPTNLPETITIIYLHDNTIKVIPPGAFSP 
                 
                     
                 
                   YKKLREIYLGSNQISELAPDAFQGLRSLNVLDLGTNKITELPKSLFEGLF 
                 
                     
                 
                   SLQELFLCCNKINCLRVDAFQDLHNLNHLALDQNKLQTIAKGTFSPLRAI 
                 
                     
                 
                   QHMYLFGNPFICDCHLKWLADYLHIAMRWDGKAVNDPDSARCTSPRRLAN 
                 
                     
                 
                   KRIGQIKSKKFRC. 
                 
             
                
               
            
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . The recombinant vector of  claim 1 , wherein an X is the amino acid tyrosine. 
     
     
         6 . The recombinant vector of  claim 1 , wherein an X is the amino acid selected from phenylalanine (Phe), tryptophan (Trp) and histidine (His). 
     
     
         7 . The recombinant vector of  claim 1 , wherein an X is the amino acid selected from asparagine (Asn) and aspartic acid (Asp). 
     
     
         8 . An expression system comprising a vector of  claim 1 .