Polymer-modified viruses

Abstract

The present invention relates to polymer-modified viruses, processes for obtaining them and their use. The invention also provides means of attaching polymer molecules to viral particles whereas retaining infectivity of the modified virus.

We claim:  
     
         1 . A polymer-modified virus comprising a virus particle having at least one polymer molecule bound thereto.  
     
     
         2 . The polymer-modified virus of  claim 1  wherein said polymer is a polyalkalene oxide or a polyalkalene glycol.  
     
     
         3 . The polymer-modified virus of  claim 1  wherein said polymer is a polyoxymethylene, polyethylene glycol, polyethylene oxide or methoxypolyethyleneglycol.  
     
     
         4 . The polymer-modified virus of  claim 1  wherein said polymer is selected from the group consisting of polymethyl-ethyleneglycol, polyhydroxypropyleneglycol, polypropylene glycol, polymethylpropylene glycol, polyhydroxypropylene oxide, and polyvinyl pyrrolidone.  
     
     
         5 . The polymer-modified virus of  claim 1  wherein said polymer is polyethylene glycol.  
     
     
         6 . The polymer-modified virus of  claim 5  wherein said polyethylene glycol has an average molecular weight of from 200 daltons to 20,000 daltons.  
     
     
         7 . The polymer-modified virus of  claim 5  wherein said polyethylene glycol has an average molecular weight of from 2000 daltons to 12,000 daltons.  
     
     
         8 . The polymer-modified virus of  claim 5  wherein said polyethylene glycol has an average molecular weight of about 5000 daltons.  
     
     
         9 . The polymer-modified virus of  claim 1  wherein said virus is retrovirus, adenovirus, adenoassociated virus, herpesvirus or poxvirus.  
     
     
         10 . The polymer-modified virus of  claim 1  wherein said virus is adenovirus.  
     
     
         11 . The polymer-modified virus of  claim 1  wherein said virus is adenovirus and said polymer is polyethyleneglycol.  
     
     
         12 . The polymer-modified virus of  claim 11  wherein said adenovirus is a recombinant adenoviral vector.  
     
     
         13 . The polymer-modified virus of  claim 1  wherein said virus is a recombinant viral vector comprising a transgene.  
     
     
         14 . The polymer-modified virus of  claim 1  wherein said polymer molecule is directly covalently bound to said virus particle.  
     
     
         15 . The polymer-modified virus of  claim 1  wherein said polymer molecule is indirectly covalently bound to said virus particle by an intermediate coupling moiety.  
     
     
         16 . The polymer-modified virus of  claim 1  wherein said polymer molecule is indirectly noncovalently attached to said virus particle.  
     
     
         17 . The polymer-modified virus of  claim 16  wherein said polymer molecule is indirectly noncovalently attached to said virus particle by a ligand.  
     
     
         18 . The polymer-modified virus of  claim 17  wherein said ligand has specificity for a viral surface component.  
     
     
         19 . The polymer-modified virus of  claim 17  wherein said ligand is an antibody.  
     
     
         20 . The polymer-modified virus of  claim 17  wherein said ligand is a non-neutralizing anti-virus antibody.  
     
     
         21 . The polymer-modified virus of  claim 17  wherein said ligand is a non-neutralizing anti-hexon antibody.  
     
     
         22 . A method of making a polymer-modified virus comprising a virus particle having at least one polymer molecule bound thereto, said method comprising activating a polymer to provide an activated polymer, and coupling said activated polymer to said virus particle.  
     
     
         23 . The method of  claim 22  wherein said polymer is activated by converting a terminal moiety of said polymer to an activated moiety, or by attaching an activated coupling moiety to said polymer.  
     
     
         24 . The method of  claim 22  wherein said activated polymer is activated polyethyleneglycol.  
     
     
         25 . The method of  claim 24  wherein said activated polyethyleneglycol is methoxypolyethylene glycol-tresylate (TMPEG), methoxypolyethylene glycol-acetaldehyde, methoxypolyethylene glycol activated with cyanuric chloride, N-hydroxysuccinimide polyethylene glycol (NHS-PEG), or polyethyleneglycol-N-succimimide carbonate.  
     
     
         26 . A method of making a polyethylene glycol-modified virus comprising a virus particle having at-least one polyethylene glycol molecule bound thereto, said method comprising coupling methoxypolyethylene glycol-tresylate to said virus particle.  
     
     
         27 . The method of  claim 26  wherein said virus is a recombinant adenoviral vector.  
     
     
         28 . The method of  claim 27  wherein said recombinant adenoviral vector contains a transgene.  
     
     
         29 . A method of making a polymer-modified virus comprising a virus particle having at least one polymer molecule bound thereto, said method comprising covalently attaching a ligand to said polymer to provide a polymer modified ligand, and incubating said polymer activated ligand with said virus particle.  
     
     
         30 . The method of  claim 29  wherein said ligand is an antibody or antibody fragment.  
     
     
         31 . The method of  claim 29  wherein said ligand is a non-neutralizing anti-virus antibody.  
     
     
         32 . The method of  claim 31  wherein said non-neutralizing anti-virus antibody is a non-neutralizing anti-hexon antibody.  
     
     
         33 . The method of  claim 29  wherein said virus is a recombinant adenoviral vector.  
     
     
         34 . The method of  claim 33  wherein said recombinant adenoviral vector contains a transgene.  
     
     
         35 . A method for introducing a transgene into a target cell comprising introducing the polymer-modified virus of  claim 13  into said target cell.  
     
     
         36 . The method of  claim 35  wherein said virus is adenovirus.  
     
     
         37 . The method of  claim 35  wherein said polymer-modified virus is introduced into said target cell by infection.  
     
     
         38 . A method for delivering a virus to a tumor comprising administering the polymer-modified virus of  claim 1  to a subject having a tumor under conditions whereby the polymer-modified virus localizes to said tumor.  
     
     
         39 . The method of  claim 38  wherein said polymer-modified virus is present in a composition with a physiologically acceptable carrier.  
     
     
         40 . A composition comprising the polymer-modified virus of  claim 1  or  12  and a carrier.