Lymphotropic agents and vectors

Abstract

Human herpes virus (HHV) 7 is capable of binding to the CD4 antigen and the HHV-7 or a binding protein derived therefrom is thus useful as a CD4-ligand for various therapeutic applications. HHV-6 or HHV-7 are lymphotropic and are thus useful as lymphotropic vectors for delivering DNA into lymphocytes.

1 . A CD4-ligand, selected from the group consisting of: 
 (a) human herpes virus 7 (HHV-7);    (b) a mutant of HHV-7 capable of binding to the CD4 receptor;    (c) a virus particle of the virus of (a) or (b);    (d) a virion polypeptide of (c) capable of binding to CD4 receptor;    (e) a fusion protein of a fragment of (d) and another protein or peptide, which is capable of binding the CD4 receptor;    (f) derivatives of any of (c), (d) or (e) obtained by chemical modification, addition, deletion or replacement of one or more amino acid residues from the protein or peptides of (c), (d) or (e) which are capable of binding to the CD4 receptor; and    (g) any combination of the agents under (a), (b), (c), (d), (e) and (f).    
     
     
         2 . A pharmaceutical composition comprising a CD4-ligand according to  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         3 . A pharmaceutical composition according to  claim 2 , for parenteral administration.  
     
     
         4 . A pharmaceutical composition according to  claim 2  or  3 , for the treatment or prophylaxis of viral diseases, in which the virus enters the cell after first binding to the CD4-receptor.  
     
     
         5 . A pharmaceutical composition according to  claim 4 , for the treatment or prophylaxis of HIV infection.  
     
     
         6 . A pharmaceutical composition according to  claim 2  or  3 , for use as an immuno-modulating agent.  
     
     
         7 . A lymphotropic vector comprising a recombinant DNA molecule having: 
 (i) a DNA sequence derived from HHV-6 or HHV-7 and comprising an origin of DNA replication, a promoter sequence capable of inducing expression in a lymphatic host cell of a downstream nucleic acid sequence and a cleavage and packaging signal;    (ii) a foreign nucleic acid sequence downstream to an expression control of said promotor sequence.    
     
     
         8 . A vector according to  claim 7 , wherein said recombinant DNA molecule is incorporated into a delivery vehicle selected from the group consisting of: 
 (a) an HHV-6 or HHV-7 particle;    (b) a mutant HHV-6 or mutant HHV-7 particle capable of infecting lymphatic cells and delivering its content of DNA to such cells;    (c) a chemically modified particle of (a) or (b) essentially retaining the ability to infect lymphatic cells; and    (d) any combination of (a), (b) or (c).    
     
     
         9 . A vector according to  claim 7  or  8 , for the treatment of prophylaxis of a lymphatic disease or disorder, wherein said foreign nucleic acid sequence encodes a product the expression of which brings to the amelioration or prevention of said diseases or disorder.  
     
     
         10 . A vector according to  claim 9 , for the treatment of HIV infection, wherein said foreign nucleic acid sequence encodes an expression product which inhibits HIV replication.  
     
     
         11 . A vector according to  claim 9 , for the treatment of lymphoma, wherein said foreign nucleic acid sequence encodes an expression product which inhibits oncogenes being expressed in the malignant lymphatic cells.  
     
     
         12 . A vector according to  claim 9 , for the treatment of lymphoma, wherein said foreign nucleic acid sequence has a sequence which is an antisense sequence to the oncogene active in the malignant lymphatic cells.  
     
     
         13 . A vector according to  claim 9 , for the treatment of lymphoma, wherein said foreign nucleic acid sequence encodes an expression product which increases the malignant cells' sensitivity to chemotherapy.  
     
     
         14 . A vector for the treatment of enzyme deficiency of lymphatic cells, wherein said foreign nucleic acid sequence encodes the deficient enzyme.  
     
     
         15  A vector according to  claim 7  or  8 , being capable of autonomous replication.  
     
     
         16 . A vector according to  claim 7  or  8 , which is not capable of self replication and is used in combination with a helper virus.  
     
     
         17 . A pharmaceutical composition comprising a vector according to any one of claims  7 - 16 .  
     
     
         18 . A method of treatment of a disease or disorder, comprising use of a CD4-ligand according to  claim 1 , a pharmaceutical composition according to any one of claims  2 - 6  or a vector according to any one of claims  7 - 16 .