Transfection agents

Abstract

The present invention provides compounds, compositions and methods that enhance the transfer of an agent into a cell. The agents can include polypeptides, polynucleotides such as genes and antisense nucleic acids, and other molecules. In some embodiments, the agents are modulating agents that can modulate a cellular activity or function when introduced into the cell. The compounds, compositions and methods are useful for introducing agents such as genes into individual cells, as well as cells that are present as a tissue or organ.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group; 
 m and n are each independently selected from about 0-2; 
 R 3  is selected from the group consisting of —NR 4 R 5  wherein R 4  and R 5  are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, an optionally substituted acyloxy, and a quaternary ammonium salt —NR 6 R 7 R 8 X wherein R 6 , R 7  and R 8  are independently a member selected from the group consisting of hydrogen and C 1 -C 4  alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate. 
 
     
     
         2 . The compound of  claim 1 , wherein R 1  and R 2  are both hydroxyl groups. 
     
     
         3 . The compound of  claim 1 , wherein m and n are each 1. 
     
     
         4 . (canceled) 
     
     
         5 . The compound of  claim 1 , wherein R 4  is hydrogen; and R 5  is a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, and an optionally substituted acyloxy. 
     
     
         6 . (canceled) 
     
     
         7 . The compound of  claim 5 , wherein R 5  is succinyl. 
     
     
         8 . The compound of  claim 5 , wherein R 5  is acyloxy. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . A composition for delivering an agent to a cell, the composition comprising the agent and a delivery enhancing compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group; 
 m and n are each independently selected from about 0-2; 
 R 3  is selected from the group consisting of —NR 4 R 5  wherein R 4  and R 5  are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, an optionally substituted acyloxy, and a quaternary ammonium salt —NR 6 R 7 R 8 X wherein R 6 , R 7  and R 8  are independently a member selected from the group consisting of hydrogen and C 1 -C 4  alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate. 
 
     
     
         12 . The composition according to  claim 11 , wherein R 1  and R 2  are both hydroxyl groups. 
     
     
         13 . The composition according to  claim 11 , wherein m and n are each 1. 
     
     
         14 . (canceled) 
     
     
         15 . The composition according to  claim 11 , wherein R 4  is hydrogen; and R 5  is a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, and an optionally substituted acyloxy. 
     
     
         16 . (canceled) 
     
     
         17 . The composition according to  claim 15 , wherein R 5  is succinyl. 
     
     
         18 . The composition according to  claim 15 , wherein R 5  is acyloxy. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The composition according to  claim 11 , wherein said agent is a diagnostic agent. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The composition according to  claim 11 , wherein said agent comprises a polynucleotide or protein. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . The composition according to  claim 11 , wherein the composition further comprises a polymeric matrix. 
     
     
         29 . The composition according to  claim 11 , wherein the composition further comprises a mucoadhesive. 
     
     
         30 . The composition according to  claim 24 , wherein said agent comprises a protein. 
     
     
         31 . The composition according to  claim 30 , wherein said protein is an interferon. 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . The composition according to  claim 30 , wherein said protein is an antibody. 
     
     
         36 . (canceled) 
     
     
         37 . A method of delivering an agent to a cell, said method comprising administering said agent to said cell in a composition comprising a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group; 
 m and n are each independently selected from about 0-2; 
 R 3  is selected from the group consisting of —NR 4 R 5  wherein R 4  and R 5  are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, an optionally substituted acyloxy, and a quaternary ammonium salt —NR 6 R 7 R 8 X wherein R 6 , R 7  and R 8  are independently a member selected from the group consisting of hydrogen and C 1 -C 4  alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate. 
 
     
     
         38 . A method of treating bladder cancer by the administration of a recombinant viral vector encoding a cytostatic or a tumor suppressor gene in combination with a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group; 
 m and n are each independently selected from about 0-2; 
 R 3  is selected from the group consisting of —NR 4 R 5  wherein R 4  and R 5  are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, and an optionally substituted acyloxy, and a quaternary ammonium salt —NR 6 R 7 R 8 X wherein R 6 , R 7  and R 8  are independently a member selected from the group consisting of hydrogen and C 1 -C 4  alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate. 
 
     
     
         39 - 75 . (canceled)