Nuclear targeting by means of bacterial proteins

Abstract

A nuclear delivery construct comprises (i) protein H or a fragment or derivative thereof that is capable of being targeted to the nucleus of a eukaryotic cell; and associated therewith (ii) one or more other components whose targeting to the nucleus of the eukaryotic cell is desired.

1 . A nuclear delivery construct comprising: (i) protein H or a fragment or derivative thereof that is capable of being targeted to the nucleus of eukaryotic cell; and associated therewith (ii) one or more other components whose targeting to the nucleus of the eukaryotic cell is desired.  
     
     
         2 . A nuclear delivery construct according to  claim 1  wherein the fragment or derivative of protein H comprises the A region of protein H, or a fragment or derivative thereof that is capable of being targeted to the nucleus of a eukaryotic cell.  
     
     
         3 . A nuclear delivery construct according to  claim 2  wherein the fragment or derivative of protein H comprises the AB region of protein H, or a derivative thereof that is capable of being targeted to the nucleus of a eukaryotic cell.  
     
     
         4 . A nuclear delivery construct according to  claim 1  comprising, as component (i) a fragment or derivative of protein H which is capable of being targeted to the nucleus of a eukaryotic cell but does not have a cytostatic effect on the cell.  
     
     
         5 . A nuclear delivery construct according to  claim 1  wherein component (ii) is a polypeptide, nucleic acid, small molecule drug or a liposome.  
     
     
         6 . A nuclear delivery construct according to  claim 5  wherein component (ii) is a polypeptide and the construct is in the form of a fusion protein.  
     
     
         7 . A nuclear delivery construct according to  claim 1  wherein components (i) and (ii) are covalently or non-covalently associated.  
     
     
         8 . A pharmaceutical composition comprising a nuclear delivery construct as defined in  claim 1;  and a pharmaceutically acceptable carrier.  
     
     
         9 . A nuclear delivery construct as defined in  claim 1  for use in a method of treatment of the human or animal body, or for use in a method of diagnosis.  
     
     
         10 - 11 . (canceled)  
     
     
         12 . A method according to  claim 22  wherein the construct is targeted to the nucleus of a cell in which nucleophosmin (NPM)/B23 is up-regulated.  
     
     
         13 . A method according to  claim 22  wherein component (i) of the construct interacts with actin, NPM/B23, protein SET or hnRNP A2/B1.  
     
     
         14 . A method according to  claim 22  wherein the cell is a tumour cell, a proliferating cell, a virus-infected cell or a lymphocyte.  
     
     
         15 - 16 . (canceled)  
     
     
         17 . A method according to  claim 22  wherein component (ii) of the construct is a nucleic acid encoding a protein, and targeting to the nucleus effects gene therapy of the cell.  
     
     
         18 . A nucleic acid sequence encoding a fusion protein according to  claim 6 .  
     
     
         19 . A vector comprising a nucleic acid sequence according to  claim 18 .  
     
     
         20 . A cell comprising a nucleic acid sequence according to  claim 18 .  
     
     
         21 . A method of producing a fusion according to  claim 6  comprising expressing a nucleic acid sequence according to  claim 18  in a cell, and recovering the fusion protein thus obtained.  
     
     
         22 . A method of treating a disease of the human or animal body by targeting a construct as defined in  claim 1  to the nucleus off a eukaryotic cell, comprising administering an effective amount of the construct to a human or animal subject.  
     
     
         23 . A method according to  claim 22  wherein the disease is a tumour or a viral infection.  
     
     
         24 . A cell comprising a vector according to  claim 19 .  
     
     
         25 . A method of targeting one or more components to the nucleus of a eukaryotic cell, said method comprising administering a nuclear delivery construct to said eukaryotic cell, wherein said nuclear delivery construct is as defined in  claim 1.