Novel virus vector

Abstract

There is provided a virus vector characterized in that a water-soluble polymer is directly or indirectly linked to a surface of a virus particle and a heterogeneous peptide having an affinity for integrin present on a surface of a target cell is linked to the water-soluble polymer.

1 . A virus vector, characterized in that a water-soluble polymer is directly or indirectly linked to a surface of a virus particle and a heterogeneous peptide having an affinity for integrin present on a surface of a target cell is linked to the water-soluble polymer.  
     
     
         2 . The virus vector according to  claim 1 , wherein said water-soluble polymer is linked to the surface of the virus particle via a linker amino acid and a linker.  
     
     
         3 . The virus vector according to  claim 1 , wherein said virus is adenovirus.  
     
     
         4 . The virus vector according to  claim 1 , wherein said water-soluble polymer is polyethylene glycol or a derivative thereof.  
     
     
         5 . The virus vector according to  claim 4 , wherein said polyethylene glycol has a molecular weight of 3000-4000.  
     
     
         6 . The virus vector according to  claim 2 , wherein said linker amino acid is cysteine and said linker is one having a linking ability to a thiol group and an amino group.  
     
     
         7 . The virus vector according to  claim 6 , wherein said linker is N-(6-maleimidocaproyloxy) succinimide (EMCS).  
     
     
         8 . The virus vector according to  claim 1 , wherein said integrin is αV β3 or αVβ5.  
     
     
         9 . The virus vector according to  claim 1 , wherein said heterogeneous peptide has a sequence containing arginine(R)-glycine(G)-aspartic acid(D).  
     
     
         10 . The virus vector according to  claim 9 , wherein said heterogeneous peptide has a sequence containing one or more of β-alanine.  
     
     
         11 . The virus vector according to  claim 9 , wherein said heterogeneous peptide contains lysine (K) and is branched via said lysine.  
     
     
         12 . The virus vector according to  claim 11 , wherein said heterogeneous peptide has an amino acid sequence: tyrosine(Y)-glycine(G)-glycine(G)-arginine(R)-glycine(G)-aspartic acid(D)-threonine(T)-proline(P)-β-alanine(X)-lysine(K)-β-alanine(X)-proline(P)-threonine(T)-aspartic acid(D)-glycine(G)-arginine(R)-glycine(G)-glycine(G)-tyrosine(Y).  
     
     
         13 . A method of gene transfer comprising using the virus vector as defined in  claim 1 .  
     
     
         14 . A method of production of a virus vector comprising steps of: 
 a) linking a linker amino acid to one terminal of a water-soluble polymer to obtain a water-soluble polymer-linker amino acid;    b) linking a heterogeneous peptide having an affinity for integrin to the water-soluble polymer of the water-soluble polymer-linker amino acid to obtain a heterogeneous peptide-water-soluble polymer-linker amino acid;    c) linking a linker to the linker amino acid of the obtained heterogeneous peptide-water soluble polymer-linker amino acid; and    d) linking the heterogeneous peptide-water-soluble polymer-linker amino acid with a virus via the linker.    
     
     
         15 . The method of production of a virus vector according to  claim 14 , wherein the steps a) and b) are conducted while the linker amino acid is linked to a resin (Resin) and, thereafter, the steps c) and d) are conducted after the produced heterogeneous peptide-water soluble polymer-linker amino acid is cut from the resin.  
     
     
         16 . The method of production of a virus vector according to  claim 14 , wherein said water-soluble polymer is polyethylene glycol or a derivative thereof.  
     
     
         17 . The method of production of a virus vector according to  claim 14 , wherein said linker amino acid is cysteine and said linker is one having a linking ability to a thiol group and an amino group.  
     
     
         18 . The virus vector according to  claim 2 , wherein said virus is adenovirus.  
     
     
         19 . The virus vector according to  claim 18 , wherein said water-soluble polymer is polyethylene glycol or a derivative thereof.  
     
     
         20 . The virus vector according to  claim 19 , wherein said polyethylene glycol has a molecular weight of 3000-4000.  
     
     
         21 . The virus vector according to  claim 20 , wherein said linker amino acid is cysteine and said linker is one having a linking ability to a thiol group and an amino group.  
     
     
         22 . The virus vector according to  claim 21 , wherein said linker is N-(6-maleimidocaproyloxy) succinimide (EMCS).  
     
     
         23 . The virus vector according to  claim 22 , wherein said integrin is αV β3 or αVβ5.  
     
     
         24 . The virus vector according to  claim 23 , wherein said heterogeneous peptide has a sequence containing arginine(R)-glycine(G)-aspartic acid(D).  
     
     
         25 . The virus vector according to  claim 24 , wherein said heterogeneous peptide has a sequence containing one or more of β-alanine.  
     
     
         26 . The virus vector according to  claim 25 , wherein said heterogeneous peptide contains lysine (K) and is branched via said lysine.