Polynucleotide compositions

Abstract

Compositions for stabilizing polynucleic acids and increasing the ability of polynucleic acids to cross cell membranes and act in the interior of a cell. In one aspect, the invention provides a polynucleotide complex between a polynucleotide and certain polyether block copolymers. The polynucleotide complex can further include a polycationic polymer, as well as suitable targeting molecules and surfactants. The invention also provides a polynucleotide complex between a polynucleotide and a block copolymer comprising a polyether block and a polycation block.

What is claimed:  
     
         1 . A polymer of a plurality of covalently bound polymer segments wherein said segments comprise: 
 (a) at least one polycation segment which is a cationic homopolymer or copolymer comprising at least three cationic amino acids, or at least three aminoalkylene monomers, said monomers being selected from the group consisting of: 
 (i) at least one tertiary amino monomer of the formula:  
                     
  and the quaternary salts of said tertiary amino monomer, and  
 (ii) at least one secondary amino monomer of the formula:  
                     
  and the acid addition and quaternary salts of said secondary amino monomer, in which: 
 R 1  is hydrogen, alkyl of 2 to 8 carbon atoms, an A monomer, or a B monomer;  
 each of R 2  and R 3 , taken independently of the other, is the same or different straight or branched chain alkanediyl group of the formula: 
 —(C z H 2z )— 
  in which z has a value of from 2 to 8;  
 R 4  is hydrogen satisfying one bond of the depicted geminally bonded carbon atom; and  
 R 5  is hydrogen, alkyl of 2 to 8 carbon atoms, an A monomer, or a B monomer;  
 R 6  is hydrogen, alkyl of 2 to 8 carbon atoms, an A monomer, or a B monomer;  
 R 7  is a straight or branched chain alkanediyl group of the formula: 
 —(C z H 2z )— 
  in which z has a value of from 2 to 8; and  
 R 8  is hydrogen, alkyl of 2 to 8 carbon atoms, an A monomer, or a B monomer; and  
 
   (b) at least one water-soluble nonionic polymer segment.    
     
     
         2 . The polymer according to  claim 1  wherein the water-soluble nonionic polymer segment is a homopolymer or copolymer of at least one of the monomers selected from the group consisting of acrylamide, gycerol, vinylalcohol, vinylpyrrolidone, vinylpyridine, vinylpyridine N-oxide, oxazoline, or a acroylmorpholine, and derivatives thereof.  
     
     
         3 . The polymer according to  claim 1  wherein the water-soluble nonionic polymer is of the formula:  
       
         
           
           
               
               
           
         
       
       in which m has a value of from 3 to about 10,000.  
     
     
         4 . The polymer according to  claim 1  wherein said water-soluble nonionic polymer segment comprises at least one straight or branched chained polyether segment having from about 5 to about 400 monomeric units which is: 
 (i) a homopolymer of a first alkyleneoxy monomer —OC n H 2n — or  
 (ii) a copolymer or block copolymer of said first alkyleneoxy monomer and a second different alkyleneoxy monomer —OC m H 2m —,  
 in which n has a value of 2 or 3 and m has a value of from 2 to 4.  
 
     
     
         5 . A composition comprising the polymer of  claim 1  and a polynucleotide.  
     
     
         6 . A composition comprising the polymer of  claim 1  and a targeting molecule.  
     
     
         7 . A composition comprising the polymer of  claim 1 , a polynucleotide and a surfactant.  
     
     
         8 . The composition according to  claim 4  wherein said surfactant is cationic, nonionic, or zwitterionic.  
     
     
         9 . A composition comprising the polymer of  claim 1  and a virus.  
     
     
         10 . A composition comprising the polymer of  claim 1  and at least one of a ligand and a receptor.  
     
     
         11 . A composition comprising the polymer of  claim 1  and at least one of biotin, avidin, and streptavidin.  
     
     
         12 . A method of treating a mammal in need of treatment comprising administering to said mammal an effective amount of the polymer of  claim 1 .  
     
     
         13 . A copolymer comprising at least one polynucleotide segment and at least one polyether segment, said polyether segment comprising oxyethylene and oxypropylene.